ORCID Profile
0000-0001-5920-4604
Current Organisations
University of Melbourne
,
University of Melbourne Faculty of Science
,
Centre for Eye Research Australia
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Publisher: Elsevier BV
Date: 06-1997
DOI: 10.1016/S0042-6989(96)00269-6
Abstract: The aim of this study was to determine whether an integrator of neural activity influences the amount of myopia and axial elongation resulting from deprivation of form vision. The effects on ocular parameters of a continuous period of 30 min per day of normal vision was compared to two exposures of 15 min duration each, or three exposures of 10 min each. For the remaining time, chicks had monocular translucent occlusion in a 12 hr light/12 hr dark diurnal cycle, for either 2 or 3 weeks. Fellow eyes and the eyes of bilaterally unoccluded chicks were used as controls. We found that several short periods of normal visual stimulation per day were more effective in preventing the development of form deprivation myopia and axial elongation than was one single period of the same total duration, after both 2 and 3 weeks of treatment. This study suggests that the level of neural activity in the retina may have a cumulative effect in influencing ocular growth.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 02-2007
DOI: 10.1167/IOVS.06-0585
Abstract: To determine whether there is an association between dietary omega-3 (omega-3) fatty acid intake, age, and intraocular pressure (IOP) caused by altered aqueous outflow. Sprague-Dawley rats were fed either omega-3-sufficient (omega-3(+)) or omega-3-deficient (omega-3(-)) diets from conception. The diets had 7% lipid content. The omega-3(+) diet contained safflower, flaxseed, and tuna oils (5.5:1.0:0.5), and the omega-3(-) diet contained safflower oil only. Intraocular pressure was measured at 5 to 40 weeks of age under light anesthesia (omega-3(+), n = 39 omega-3(-), n = 48). Aqueous outflow was determined at 45 weeks in a subgroup of animals (omega-3(+), n = 15 omega-3(-), n = 22) using pulsed infusion. Ciliary body tissues (n = 6 per group) were assayed for fatty acid content by thin-layer and gas-liquid chromatography in both diet groups. Animals raised on omega-3(+) diets had a 13% decrease in IOP at 40 weeks of age (13.48 +/- 0.32 mm Hg vs. 15.46 +/- 0.29 mm Hg P < 0.01). When considered as a change in IOP relative to 5 weeks of age, the omega-3(+) group showed a 23% decrease (P < 0.001). This lower IOP in the omega-3(+) diet group was associated with a significant increase (+56% P < 0.001) in outflow facility and a decrease in ocular rigidity (-59% P < 0.001). The omega-3(+) group showed a 3.3 times increase in ciliary body docosahexaenoic acid (P < 0.001). Increasing dietary omega-3 reduces IOP with age because of increased outflow facility, likely resulting from an increase in docosanoids. This indicates that dietary manipulation may provide a modifiable factor for IOP regulation. However, further studies are needed to consider whether this can modify the risk for glaucoma and can play a role in treatment of the disease.
Publisher: Elsevier BV
Date: 04-2002
DOI: 10.1016/S0042-6989(02)00033-0
Abstract: We investigated the effect that spatially coincident luminance increments (luminance pedestals) have on flicker thresholds at several eccentricities and target sizes. Luminance pedestals elevated flicker litude-thresholds more when stimuli were presented eccentrically, both at low (4 Hz) and high (20 Hz) temporal frequencies. Altering the size of the eccentric stimulus failed to equate central and eccentric thresholds at all pedestal litudes. Comparisons with flicker thresholds at various background luminances suggests that the increase in luminance-pedestal flicker thresholds peripherally is due to increased suppressive rod-cone interactions, increased effectiveness of luminous contrast on edge-sensitive flicker mechanisms, as well as increased gain in the light adaptation response.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 08-2007
DOI: 10.1167/IOVS.06-1278
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.PLEFA.2006.03.010
Abstract: Failure to provide omega 3 fatty acids in the perinatal period results in alterations in nerve growth factor levels, dopamine production and permanent elevations in blood pressure. The present study investigated whether changes in brain (i.e., hypothalamus) glycerophospholipid fatty acid profiles induced by a diet rich in omega 6 fatty acids and very low in alpha-linolenic acid (ALA) during pregnancy and the perinatal period could be reversed by subsequent feeding of a diet containing ALA. Female rats (6 per group) were mated and fed either a low ALA diet or a control diet containing ALA throughout pregnancy and until weaning of the pups at 3 weeks. At weaning, the pups (20 per group) remained on the diet of their mothers until 9 weeks, when half the pups were switched onto the other diet, thus generating four groups of animals. At 33 weeks, pups were killed, the hypothalamus dissected from the male rats and analysed for glycerophospholipid fatty acids. In the animals fed the diet with very little ALA and then re-fed the control diet containing high levels of ALA for 24 weeks, the DHA levels were still significantly less than the control values in PE, PS and PI fractions, by 9%, 18% and 34%, respectively. In this group, but not in the other dietary groups, ALA was detected in all glycerophospholipid classes at 0.2-1.7% of the total fatty acids. The results suggest that omega 6-3 PUFA imbalance early in life leads to irreversible changes in hypothalamic composition. The increased ALA and reduced DHA proportions in the animals re-fed ALA in later life are consistent with a dysfunction or down-regulation of the conversion of ALA to 18:4n-3 by the delta-6 desaturase.
Publisher: SAGE Publications
Date: 16-07-2012
Abstract: Purpose: People with migraine often report aversion to flickering lights and show abnormal results on behavioural tasks that require the processing of temporal visual information. Studies have reported that the cortically evoked electrophysiological response to a flickering visual stimulus is abnormal however, none have considered whether there is an underlying pre-cortical abnormality. In this cross-sectional study, we consider whether people with migraine have retinal and cortical electrophysiological abnormalities to flickering stimuli. Methods: Monocular transient (1 Hz) and steady-state (8.3 Hz) pattern reversal electroretinograms (PERGs) and pattern visual evoked responses (PVERs) were measured simultaneously in 45 people with migraine (26 without aura, 19 with aura) and 30 non-headache controls at a time between migraine attacks. Results: PERG litude and timing did not differ significantly between groups. Transient PVER litude was significantly reduced (28%) in the migraine with aura group compared to the controls F(2,72) = 3.6, p = 0.03). Both migraine groups showed significant reductions (32%, 39%) in steady-state PVER litude relative to controls (F(2,70) = 4.3, p = 0.02). Conclusions: This study finds normal retinal processing of flickering stimuli in the presence of abnormal cortical function between migraine attacks.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Wiley
Date: 04-2003
DOI: 10.1007/S11745-003-1084-Y
Abstract: Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. Previous work in both animals and humans with high blood pressure has demonstrated the antihypertensive effects of n-3 polyunsaturated fatty acids (PUFA), although it is not known whether these nutrients are effective in preventing hypertension. The predominant n-3 PUFA in the mammalian nervous system, docosahexaenoic acid (DHA), is deposited into synaptic membranes at a high rate during the perinatal period, and recent observations indicate that the perinatal environment is important for the normal development of blood pressure control. This study investigated the importance of perinatal n-3 PUFA supply in the control of blood pressure in adult Sprague-Dawley rats. Pregnant rat dams were fed semisynthetic diets that were either deficient in (DEF) or supplemented with (CON) n-3 PUFA. Offspring were fed the same diets as their mothers until 9 wk then, half of the rats from each group were crossed over to the opposite diet creating four groups, i.e., CON-CON CON-DEF DEF-DEF, DEF-CON. Mean arterial blood pressures (MAP) were measured directly, at 33 wk of age, by cannulation of the femoral artery. The phospholipid fatty acid profile of the hypothalamic region was determined by capillary gas-liquid chromatography. The tissue phospholipid fatty acid profile reflected the diet that the rats were consuming at the time of testing. Both groups receiving DEF after 9 wk of age (i.e., DEF-DEF and CON-DEF) had similar profiles with a reduction in DHA levels of 30%, compared with rats receiving CON (i.e., CON-CON and DEF-CON). DEF-DEF rats had significantly raised MAP compared with all other groups, with differences as great as 17 mm Hg. DEF-CON rats had raised MAP compared with CON-CON rats, and DEF-DEF rats had higher MAP than CON-DEF rats, despite the fact that their respective fatty acid profiles were not different. These findings indicate that inadequate levels of DHA in the perinatal period are associated with altered blood pressure control in later life. The way in which these long-term effects are produced remains to be elucidated.
Publisher: Elsevier BV
Date: 06-2012
DOI: 10.1016/J.NEUROBIOLAGING.2011.11.026
Abstract: Advancing age is a major risk factor for many neurodegenerative diseases but the underlying pathophysiology is not clear. We hypothesize that aging impairs the ability of neurons in the central nervous system to recover functionally after injury. To test this in retinal ganglion cells in vivo, we developed an optic nerve "stress test" which monitors the functional capacity of the optic nerve and retina, during and after a subischemic injury induced by intraocular pressure elevation. We report that older (18-month) C57BL/6J mice suffered greater loss of inner retinal function compared with younger adult mice following intraocular pressure (IOP) challenge. To investigate whether age-related vulnerability to IOP challenge can be modified, we subjected 12-month-old mice to dietary restriction (DR) (alternate-day fasting) for 6 months. Compared with age-matched ad libitum fed controls, DR mice showed greater recovery in inner retinal function following IOP challenge. DR was associated with reduced oxidative stress level following injury and improved mitochondrial oxidative phosphorylation enzyme activity compared with ad libitum controls. Taken together, this study provides in vivo evidence that DR improves functional recovery of the retina following injury and points to the potential benefits of therapies that target mitochondria for the protection of the aging retina and optic nerve against injury.
Publisher: Wiley
Date: 11-11-2013
DOI: 10.1111/CEO.12247
Abstract: A novel, ultra-low energy nanosecond laser (retinal rejuvenation therapy) has been developed with the aim to slow progression of early age-related macular degeneration (AMD). The safety, changes in fundus characteristics and macular function in a cohort of participants with bilateral intermediate AMD are reported. Prospective non-randomised, pilot intervention study. Subjects with bilateral intermediate AMD (n = 50, aged 50-75 years). Ultra-low energy laser pulses applied in 12 spots around the macula of one eye (0.15-0.45 mJ), using 400 μm diameter spot, 3 nanosecond pulse length, 532 nm wavelength and energy titrated to each patient. Best corrected visual acuity, drusen area and macular sensitivity (flicker perimetry) at baseline and at 3, 6 and 12 months post-laser. Treatment was painless with no clinically visible lesions. No participant developed choroidal neovascularization, while two with thin central retinal thickness at baseline developed atrophy at 12-month follow up. Drusen area was reduced in 44% of treated eyes and 22% of untreated fellow eyes, with changes in drusen and function not being coincident. Improvement in flicker threshold within the central 3° was observed in both the treated and untreated fellow eyes at 3 months post-laser. Of the 11 eyes at greatest risk of progression (flicker defect >15 dB), seven improved sufficiently to be taken out of this high-risk category. A single unilateral application of nanosecond laser to the macula produced bilateral improvements in macula appearance and function. The nanosecond retinal rejuvenation therapy laser warrants ongoing evaluation as an early intervention for AMD.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 12-2004
DOI: 10.1167/IOVS.04-0842
Abstract: To investigate the onset of retinal neural dysfunction in the streptozotocin (STZ)-induced diatebic rat. A cohort of 20 Sprague-Dawley rats were randomly assigned to treatment (STZ 50 mg/kg, n = 10) and control (citrate buffer, n = 10) groups and observed for 12 weeks. Diabetes was confirmed by blood glucose (>15 mmol/L) and HBA(1c) (>7.0%). Treated animals received 2 to 3 U insulin daily. Retinal function was monitored using paired-flash electroretinograms (ERGs) at baseline and various time points between 2 days and 12 weeks after treatment, to allow isolation of rod and cone components. Protocols compared photoreceptor and inner retinal responses (rod and cone) at each time point. Losses in the function of rod photoreceptors and the inner retina were seen 2 days after STZ injection, with recovery in some components by 4 weeks and a secondary loss of function at 12 weeks. Some inner retinal responses (cone response and rod oscillatory potentials (OPs) remained consistently depressed over the entire 12 weeks. Retinal neural dysfunction was observed as early as 2 days after STZ injection. These acute changes reflect either STZ toxicity or hyperglycemia as a result of pancreatic compromise. Consistent loss over the 12 weeks of the cone response and OPs suggests a vulnerability of the inner retina to STZ-related effects. The 12-week losses in function of retinal neurons are consistent with a generalized diabetic neuropathy, since impaired function developed simultaneously in both inner and outer retinal neurons.
Publisher: Springer Science and Business Media LLC
Date: 09-1993
DOI: 10.3758/BF03204528
Publisher: Elsevier BV
Date: 03-2008
DOI: 10.1016/J.JNEUMETH.2007.12.007
Abstract: We characterised the dynamics in the oscillatory potentials (OPs) of the rat electroretinogram (ERG) using a continuous complex Morlet wavelet transform. Dark-adapted (>12h) full field ERG responses were recorded from five anaesthetized (ketamine:xylazine, 60:5mg/kg) adult Long-Evans rats (10-12weeks). Five responses were obtained for brief LED flashes (1-4ms) in a ganzfeld at exposures ranging from -4.2 to 1.58logcdsm(-2). Signals were recorded across a bandwidth of 0.3-1kHz and digitized at 10kHz. Morlet wavelets with frequencies between 50 and 250Hz were correlated with raw ERG signals at 1ms intervals. The litude of the correlation at each time and frequency was given by the modulus of the complex wavelet response. Candidate OPs were identified as local peaks within 10% of the maximum litude. As flash exposure increased, the litude of the OP response increased, the peak OP occurred earlier, and the peak OP frequency increased. OPs at brighter flashes clustered into two groups, peaking at 50ms in the 70 and 130Hz band for moderate intensities, and peaking at 20ms in the 70Hz band and 50ms in the 120Hz band for the highest intensities (>0logcdsm(-2)). These dynamics agree with physiological, pharmacological and clinical studies that suggest several distinct neural mechanisms contribute to OPs. Wavelet analysis reveals important dynamics in OP data that are not evident with traditional analytical approaches.
Publisher: Informa UK Limited
Date: 11-1990
Publisher: Informa UK Limited
Date: 2011
DOI: 10.1111/J.1444-0938.2010.00546.X
Abstract: Glaucoma is a leading cause of blindness. It is a multifactorial condition, the risk factors for which are increasingly well defined from large-scale epidemiological studies. One risk factor that remains controversial is the presence of diabetes. It has been proposed that diabetic eyes are at greater risk of injury from external stressors, such as elevated intraocular pressure. Alternatively, diabetes may cause ganglion cell loss, which becomes additive to a glaucomatous ganglion cell injury. Several clinical trials have considered whether a link exists between diabetes and glaucoma. In this review, we outline these studies and consider the causes for their lack of concordant findings. We also review the biochemical and cellular similarities between the two conditions. Moreover, we review the available literature that attempts to answer the question of whether the presence of diabetes increases the risk of developing glaucoma. At present, laboratory studies provide robust evidence for an association between diabetes and glaucoma.
Publisher: Informa UK Limited
Date: 12-11-1998
DOI: 10.1111/J.1444-0938.1998.TB06743.X
Abstract: Background: The Medmont AT-20 has incorporated a contrast threshold test using a predetermined letter size that can be applied in clinical settings. This paper describes a pilot study that evaluates this technology and the effects of certain parameters on test outcomes. Methods: A photometric calibration of the test was performed to define the relationship between the AT-20 scale and Weber contrast (W%). We determined the effects of repeated measures (precision), target size (6/6 to 6/96), viewing duration (50 to 1,000 msec), defocus (+0.50 to +1.50 DS) and a macula scotoma on thresholds. The accuracy of the staircase (PEST) procedure was evaluated with and without false-negative responses. Results: The AT-20 scale has an almost linear relationship to a logarithmic transformation of W% and provides a suitable measure of contrast threshold. In the absence of monitor calibration, threshold uncertainty could be as great as 0.22 log units (W%) compared with published norms. We found that threshold variability averaged +/- 7.1 AT-20 scale units (95 per cent limits of agreement) and was proportional to threshold magnitude. One dioptre of defocus decreased thresholds by about one log unit (W%) for a 6/24 target. We propose that a 6/24 letter shown for 500 msec should provide a useful target for most clinical settings. The PEST procedure can yield endpoints in 47 (+/-12) seconds, is robust to false negative (FN) responses and gives abnormal thresholds in the presence of a macula scotoma. Conclusions: The Medmont AT-20 contrast test provides a useful clinical measure of contrast threshold. With calibration, the test could also be applied to research projects.
Publisher: Wiley
Date: 24-10-2007
DOI: 10.1111/J.1463-5224.2007.00485.X
Abstract: To record intraocular pressure (IOP) of three different dog breeds following administration of one drop of 1% tropicamide. Three dog breeds -- Golden Retrievers (n = 20), Siberian Huskies (n = 20) and English Cocker Spaniels (n = 36) -- were studied. IOPs were measured using a Tonopen following corneal anesthesia with a single drop of 0.5% proxymetacaine. A drop of 0.5% tropicamide was then administered bilaterally and a second IOP measurement was taken 30 min later (postdilation). The difference between the two measurements was considered as the effect of mydriasis on IOP. Dogs had an average IOP of 14.9 +/- 3.2 mmHg, with 95% confidence limits ranging from 8 to 22 mmHg. There were significant differences between breeds (P < 0.006) with Siberian Huskies having higher IOPs (17.2 +/- 3.7 mmHg) than the other breeds (Spaniels: 14.2 +/- 2.8 mmHg, P < 0.01 Retrievers: 14 +/- 1.9 mmHg, P < 0.001). The majority (60%) of dogs displayed 5 mmHg or less in IOP change postmydriasis. Siberian Huskies showed the highest IOP levels, and also had the greatest variability with dilation. Interbreed variability in effect of tropicamide of canine IOP is evident.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-1999
DOI: 10.1097/00006324-199908000-00028
Abstract: Automated perimetry is often associated with lengthy test times when a staircase algorithm is applied. This arises because the fixed step sizes used during threshold estimation (e.g.,4/2 dB) yield reduced test efficiency, with test times being dependent on the relative positioning of the start and endpoints, as well as the step size. Neighborhood logic may speed up the process, although several presentations are still required for normal threshold values and many more presentations are required for abnormal values. We consider whether there is any justification for using a fixed step size during the threshold procedure. We show how empirical data can be applied, within a Bayesian framework, to reduce test time with little or no loss of accuracy. Finally, we demonstrate the effect that the starting probability density function can have on test efficiency by implementing an empirically determined and bimodal probability density function that provides fast outcomes.
Publisher: Springer Science and Business Media LLC
Date: 1999
Abstract: We describe the postnatal development of the electroretinogram (ERG) receptoral response in the guinea pig. In addition, the time course and nature of maturation was compared between albino and pigmented strains to consider the role that melanogenesis might have in this process. Electroretinograms were collected on groups of albino and pigmented animals from postnatal day (PD) PD1 to PD60. A-wave litudes and implicit times were extracted from filtered data (0-75 Hz). Receptoral components were modelled using the delayed gaussian model of Hood and Birch [1] fitted as an ensemble to the raw data. Guinea pigs show saturated litudes (RmP3) that are 50% of adult values at birth, these mature by PD12. Receptoral delay (t(d)) also undergoes some postnatal maturation, while phototransduction gain (log S) is adult-like at birth. Albino animals had significantly (p<0.05) larger RmP3 and log S across all ages. Guinea pigs have significant postnatal development in their receptoral response. Maturation of RmP3 implies a postnatal increase in rod outer segment length. Whereas the adult values of log S implies a mature phototransduction process at birth. We argue that the likely cause for the larger log S of albino eyes is compatible with theories of increased levels of internal light. Whereas the larger RmP3, even after allowing for increased light effectiveness, may reflect a lower ocular resistance in albino eyes due to their lower levels of melanin. Furthermore, decreased RmP3 and log S with age is observed in the pigmented group only and is consistent with increased ocular resistance due to melanin development in this strain.
Publisher: Frontiers Media SA
Date: 17-11-2016
Publisher: Elsevier BV
Date: 03-2022
DOI: 10.1016/J.AJO.2021.09.003
Abstract: The aim of this study was to determine the short-term compliance with regular home monitoring of macular retinal sensitivity (RS) in intermediate age-related macular degeneration (iAMD). Home-based outcomes were compared with in-clinic outcomes determined using (1) the same tablet device under supervision, and (2) the Macular Integrity Assessment (MaIA) microperimeter. Single-center longitudinal compliance and reliability study. A total of 73 participants with iAMD were trained to perform macular field testing with the Melbourne Rapid Fields-macular (MRF-m) iPad application. Volunteers were asked to return 6 weekly tests from home, guided by audio instructions. We determined compliance with weekly testing and surveyed for factors that limited compliance. Test reliability (false positive, false negative) and RS were compared to in-clinic assays (MaIA). Data are given as mean ± SD or as median [quartile 1-3 range]. Group comparisons were achieved with bootstrap to define the 95% confidence limits. A total of 59 participants submitted 6 home examinations with a median intertest interval of 8.0 [7.0-17] days. Compliance with weekly testing (7 days ±24 hours) was 55%. The main barrier to compliance was information technology (IT) logistic reasons. Of 694 home examinations submitted, 96% were reliable (false-positive results <25%). The mean RS returned by the tablet was significantly higher (+3.2 dB, P < .05) compared to the MaIA. Home monitoring produces reliable results that differ from in-clinic tests because of test design. This should not affect self-monitoring once an at-home baseline is established, but these differences will affect comparisons with in-clinic outcomes. Reasonable compliance with weekly testing was achieved. Improved IT support might lead to better compliance.
Publisher: Springer Science and Business Media LLC
Date: 11-09-2009
DOI: 10.1007/S10633-009-9191-8
Abstract: The aim of the study is to determine whether dimethyl sulphoxide (DMSO), a common laboratory solvent, impacts retinal function. Long Evans rats (n = 17) were intravitreally injected with five different doses of DMSO representative of those reported in the literature and spanning over 3 log units of vitreal concentration (0.01-8%). Retinal function was evaluated 1 h after injection using electroretinograms, and the waveform was decomposed into outer (photoreceptor), middle (ON-bipolar cell) and inner retinal (amacrine and ganglion cell) components. DMSO induces a dose-dependent decrease in retinal function for concentrations of 0.6% or more which is retinal layer specific. The photoreceptors of the outer retina returned normal responses at all doses (P > 0.05), whereas the mid-retinal bipolar cell response showed dose-dependent losses ranging from 21 +/- 1 to 82 +/- 1% (0.6-8% DMSO P < 0.05). In a similar dose-dependent fashion, the inner retinal response was also affected by DMSO (0.6-8%: 23 +/- 12 to 98 +/- 3% loss, P < 0.05). A single dose of DMSO < or =0.1% (2.96 x 10(-5) microM) may be safely used to dilute compounds injected into the vitreous of a rat eye. Higher doses produce short-term (at least 24 h) retinal dysfunction.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 08-2008
DOI: 10.1167/IOVS.08-1679
Abstract: Diabetes is known to alter retinal function, as measured with the electroretinogram (ERG), which shows a propensity toward inner retinal oscillatory potential (OPs) abnormalities. However, the effect that diabetes has on other ganglion cell-related responses is not known. This study was a systematic evaluation of streptozotocin (STZ) diabetes-related ERG changes in rats for the first 11 weeks after diabetogenesis. Thirty Sprague-Dawley rats were randomly assigned to treated (50 mg/kg STZ (n = 16) and control groups (1 mL/kg citrate buffer, n = 14) at 6 weeks of age. Two control animals and four STZ animals were excluded because of blood glucose criteria or systemic complications. Diabetic animals were given daily SC injections of 1 to 2 units of long-acting insulin. ERGs were measured at 4, 8, and 11 weeks after treatment. The a-wave was used as an index of outer retinal function, whereas the b-wave, OPs, and the scotopic threshold response (STR) were used as indices of inner retinal function. Photoreceptoral (a-wave) and bipolar cell (b-wave) responses were not significantly reduced by STZ treatment. OPs were significantly reduced by 8 weeks (-25% +/- 7%, P < 0.05). The most severely affected component was the ganglion cell-dominated positive STR, which was significantly decreased from the first time point (-51% +/- 11% at 4 weeks, P < 0.05), but the negative component was unaffected over the 11-week period. The ganglion cell dominated pSTR showed large losses in STZ treated rats.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-1995
DOI: 10.1097/00006324-199508000-00002
Abstract: We considered whether the color discrimination of mild color defectives scoring or = 5 in these regions is a good indicator of abnormal color discrimination. Some 30% of mild defectives (TES < or = 100) have limited hue discrimination in the red-green domain, so both the TES and error profiles need to be considered when providing vocational guidance.
Publisher: Wiley
Date: 05-1998
DOI: 10.1111/J.1442-9071.1998.TB01353.X
Abstract: Automated perimetry is associated with lengthy test times, but Baysean predictions can be applied to speed up testing. A critical component of such methods is the starting probability density function (PDF). In the present study we show that a unimodal PDF, suggested n the literature as adequate for clinical data, fails to describe the thresholds of diseased eyes and we develop a bi-modal PDF representative of a clinical population. We suggest that the implementation of a bi-modal PDF will save test time and retain test accuracy.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 19-05-2014
Abstract: The visual system rapidly adapts to contrast changes, often with each fixation. One key anatomical site underpinning contrast adaptation is the retinal ganglion cell dendrites, where degenerative changes occur in glaucoma. This study investigated the effects of early glaucoma and aging on rapid contrast adaptation. Contrast detection and discrimination thresholds were measured in central vision for briefly presented (94 ms) Gabor patches with and without adaptation to 50% contrast Gabor patches (1000 ms). Fourteen people with glaucoma (aged 58-77 years), 17 age-similar controls (aged 50-72 years), and 19 younger adults (aged 20-31 years) participated. Detection thresholds were measured at various time points (47, 106, 200, 400, 600, and 1000 ms) post adaptation. Discrimination thresholds were measured post adaptation relative to a reference contrast below (30%), equivalent to (50%), or above (70%) the adaptor. The glaucoma group demonstrated elevated unadapted detection (P < 0.0001) and discrimination (P = 0.01) thresholds relative to age-similar controls. In normal observers, aging elevated unadapted thresholds (detection: P < 0.0001 discrimination: P < 0.0001). At 47 ms post adaptation, the glaucoma group demonstrated reduced effects of adaptation relative to controls (P = 0.009). Adaptation was also reduced when the reference contrast (50%) was equivalent to the adaptor (P = 0.02). Aging did not alter adaptation of normal observers. Glaucoma alters rapid contrast adaptation while aging does not. Contrast adaptation is key to visual processing in natural visual environments. Our results imply that glaucoma produces abnormalities in natural visual experiences in central vision.
Publisher: Wiley
Date: 20-02-2013
DOI: 10.1002/CNE.23284
Abstract: The rd1 mouse is a well-established animal model for human retinitis pigmentosa (RP). We used electroretinography (ERG) to evaluate retinal function and postembedding immunocytochemistry to determine the changes in cellular amino acid expression in the normal (C57Bl6) and degenerating mouse retina (rd1), as a function of age during development and the onset of degeneration. In the normal mouse retina, photoreceptoral and post-photoreceptoral ERG responses improved simultaneously from eye-opening until adult levels were achieved at approximately postnatal day (P) 30. Maturation of amino acid neurochemistry preceded the development of retinal function in the normal retina. Amino acid levels increased immediately from birth and reached stable levels by eye-opening. In contrast, in the rd1 mouse, both rod and cone pathway function rapidly reduced from eye-opening and by P21 became undetectable. Interestingly, at P18 cone responses were still comparable between the normal and degenerating retina. Before eye opening, the pattern of amino acid immunoreactivity in the rd1 retina was similar to the normal retina. Alterations in neurochemistry were observed after the onset of rod photoreceptor cell death. The most obvious change was the reduction in neurotransmitter immunoreactivity within the synaptic layers and some cell classes of the rd1 retina. Reduction of glutamine and glutamate was observed in Müller cells before established gliosis markers. Overall, these results suggest the rapid maturation of neurochemistry by eye opening followed by functional maturation by P30 in the normal retina. The dystrophic retina displays similar neurochemistry to control retina before eye opening but a subsequent decline.
Publisher: Informa UK Limited
Date: 2002
Publisher: Wiley
Date: 04-1999
DOI: 10.1046/J.1440-1606.1999.00158.X
Abstract: Flicker deficits have been reported in various maculopathies, including age-related macular degeneration. We test whether flicker losses exist in patients with central serous chorioretinopathy (CSC) and whether the size and flicker frequency of the target is important in detecting such losses. We examined four CSC patients with temporal modulation (flicker perception) perimetry using the Medmont auto-flicker module (Medmont Pty Ltd, Melbourne, Vic. Australia), as well as static perimetry and colour vision. One case was examined using sophisticated laboratory equipment to precisely measure their temporal contrast sensitivity function (temporal CSF or de Lange curve) using larger targets to consider the effect of target frequency and size. Two patients were followed longitudinally and tested after resolution of the maculopathy. We compared our patients with an age-matched control group of 11 people. Temporal modulation perimetry detected larger and more localized defects in all cases of active CSC compared with static perimetry. There appeared to be size and frequency tuning to the deficit, with greatest loss being found at 16 Hz with small (0.5 degree) targets. The losses resolved in one case where the retina recovered in 4 weeks, but remained to a lesser degree in another case who suffered a 2 year long fluctuating course before the CSC subsided. Temporal modulation perimetry detects a loss of flicker sensitivity in patients with CSC. Deeper and more clearly defined scotomata are found with a flickering stimulus compared with a steady state one. The greatest losses of flicker sensitivity are found with 16 Hz modulation and with small targets located directly over the lesion. The duration of the disease may be important for recovery of flicker sensitivity. Temporal modulation perimetry appears to be a valuable tool for the confirmation of functional loss due to CSC.
Publisher: Elsevier BV
Date: 09-2001
DOI: 10.1016/S0042-6989(01)00139-0
Abstract: By systematically manipulating the luminance of a flickering spot and the area immediately surrounding it, we investigated why thresholds from flickering stimuli that cause a change in average luminance are elevated relative to those from stimuli with no luminance change. Threshold elevation resulted from local light adaptation and from temporal-frequency-specific interactions between the spot and its surround: at low frequencies, the contrast between the spot and the surround elevated thresholds, whereas at high frequencies, dark adaptation within the surround elevated thresholds. Our findings suggest that two common ways of determining temporal sensitivity may give markedly different outcomes.
Publisher: Elsevier BV
Date: 09-1996
DOI: 10.1016/0042-6989(95)00319-3
Abstract: Saturation discrimination has been reported to be affected early in the course of a disease. Our empirical data show a compressive curvi-linear relationship between opponent/nonopponent channel activity and saturation thresholds in normal trichromatic observers. This relationship can be explained by a model based on the Hurvich and Jameson saturation coefficient (1957), Psychology Reviews, 64, 384-404. The model considers effects of both selective and nonselective channel losses on saturation processing based on the assumption that disease produces elevated thresholds while maintaining normal psychometric response functions. Both the model and data support clinical observations of saturation losses occurring early in disease. However, the results also indicate that saturation may not be the best modality for monitoring long-term progression of such conditions. We suggest that the different processing characteristics for blue-yellow thresholds may yield added information for saturation testing under some circumstances and that saturation processing occurs at a higher cortical level.
Publisher: MDPI AG
Date: 25-07-2022
DOI: 10.3390/JCM11154317
Abstract: Background: Our primary aim is to quantify test reliability and compliance of glaucoma patients to a weekly visual field telemedicine (VFTM) schedule. A secondary aim is to determine concordance of the VFTM results to in-clinic outcomes. Methods: Participants with stable glaucoma in one eye were recruited for a 12 month VFTM trial using the Melbourne Rapid Fields (MRF-home, MRFh) iPad application. Participants attended routine 6 month clinical reviews and were tasked with weekly home monitoring with the MRFh over this period. We determined compliance to weekly VFTM (7 + 1 days) and test reliability (false positives (FPs) and fixation loss (FL) %). A secondary aim considered concordance to in-clinic measures of visual field (MRF-clinic (MRFc) and the Humphrey Field Analyzer (HFA)) in active participants (≥10 home examinations and 5 reliable HFA examinations). The linear trend in the MRFh mean deviation (MD) was compared to the HFA guided progression analysis (GPA) using Bland–Altman methods. Data are shown as the mean ± standard deviation. Results: Forty-seven participants with a mean age of 64 ± 14.6 years were recruited for the trial. The VFTM uptake was 85% and compliance to weekly home monitoring was 75% in the presence of weekly text reminders in the analysed group (n = 20). The analysed group was composed of test subjects with five reliable in-clinic HFA examinations (GPA analysis available) and who submitted a minimum of 10 MRFh examinations from home. Of the 757 home examinations returned, approximately two-thirds were reliable, which was significantly lower than the test reliability of the HFA in-clinic (MRFh: 65% vs. HFA: 85%, p 0.001). The HFA-GPA analysis gave little bias from the MRFh slope (bias: 0.05 dB/yr, p 0.05). Two eyes were found to have clinical progression during the 12 month period, and both were detected by VFTM. Conclusions: VFTM over 12 months returned good compliance (75%) to weekly testing with good concordance to in-clinic assays. VFTM is a viable option for monitoring patients with glaucoma for visual field progression in between clinical visits.
Publisher: SAGE Publications
Date: 18-03-2016
Abstract: People with migraine show increased surround suppression of perceived contrast, a perceptual analogue of centre-surround antagonistic interactions in visual cortex. A proposed mechanism is that cortical ‘hyperexcitability’ or ‘hyperresponsivity’, a prominent theory in the migraine literature, drives abnormal excitatory-inhibitory balance to give increased local inhibition. The purpose of this cross-sectional study was to determine whether cortical hyperresponsivity and excitatory-inhibitory imbalance manifests in the visual cortical response of migraine sufferers. Interictal steady-state visual evoked potentials (VEPs) in response to 0 to 97% contrast were recorded in 30 migraine participants (15 without aura, 15 with aura) and 21 non-headache controls. Monotonicity indices were calculated to determine response saturation or supersaturation. Contrast gain was modelled with a modified saturating hyperbolic function to allow for variation in excitation and inhibition. A greater proportion of migraine participants (43%) than controls (14%) exhibited significant VEP supersaturation at high contrast, based on monotonicity index (chi-square, p = 0.028). Supersaturation was also evident by the trend for greater suppressive exponent values in migraine compared to control in iduals (Mann-Whitney rank sum, p = 0.075). Supersaturation in migraine is consistent with excess excitation (hyperresponsivity) driving increased network inhibition and provides support for excitatory-inhibitory imbalance as a pathophysiological disturbance in migraine.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 11-2003
DOI: 10.1167/IOVS.03-0023
Abstract: To investigate the accuracy and precision of threshold estimates returned by two Bayesian perimetric strategies, staircase-QUEST or SQ (a Swedish interactive threshold algorithm [SITA]-like strategy) and ZEST (zippy estimation by sequential testing), and to compare these measures with those of the full-threshold (FT) algorithm. A computerized visual field simulation model was developed to compare the performance (accuracy, precision, and number of presentations) of the three algorithms. SQ implemented aspects of the SITA algorithm that are in the public domain. The simulation was tested by using standard automated perimetry (SAP) visual field data from 265 normal subjects and 163 observers with glaucomatous visual field loss and by exploring the effect of response variability and response errors on algorithm performance. SQ was faster than FT or ZEST, with a comparable mean error when simulating field tests on patients. Point-wise analysis revealed similar error and standard deviation of error as a function of threshold for FT and SQ. If the initial estimate of threshold for either procedure was incorrect, the means and standard deviations of the error increased markedly. ZEST produced more accurate thresholds than did the other two strategies when the initial estimate was removed from the true threshold. When simulated patients made errors, the accuracy and precision of sensitivity estimates were poor when the initial estimate of threshold either overestimated or underestimated the true threshold. This was particularly so for FT and SQ. ZEST demonstrated more consistent error properties than the other two measures.
Publisher: Elsevier BV
Date: 08-2003
DOI: 10.1016/S0014-4835(03)00132-5
Abstract: We wanted to determine the characteristics associated with electrophysiological and neurochemical changes secondary to ischemic insult as well as correlate these electrophysiological and neurochemical changes. A Ganzfeld source was used to elicit electroretinograms in anesthetized adult Sprague-Dawley rats. Following baseline recordings, one eye was removed for control quantitative amino acid immunocytochemistry, and ischemic insult was induced by cervical dislocation. Following the induction of ischemia, a single electroretinogram signal was collected at 1, 2, 4, 6, 8, 16, 32 or 64 min, after which the eye was removed for immunocytochemistry. The post-receptoral b-wave was undetectable after 1 min post-ischemia, whereas phototransduction declined more gradually and persisted for up to 16 min post-mortem. Both phototransduction saturated litude and sensitivity decayed with a similar time course (tc=3.06 (2.73, 3.48) versus 3.29 (2.61, 4.62)min). Significant elevation of amino acid neurotransmitter levels was not observed until 6 min post-mortem. Between 8 and 16 min post-ischemia, glutamate and GABA were significantly accumulated in neurons and Müller cells (p<0.05). Beyond 16 min, the neurotransmitter elevation in neurons and Müller cells was relatively attenuated. Aspartate immunoreactivity was significantly elevated at 4 and 6 min post-ischemia in neurons, prior to a change in any other amino acid. Moreover, of the amino acids assessed the post-ischemic change in aspartate immunoreactivity showed the best correlation with phototransduction decay (r2=0.68). Our findings show that complete impairment of phototransduction coincides with the accumulation of amino acid neurotransmitter. The correlation of aspartate immunoreactivity and phototransduction provides evidence of heightened glutamate oxidation during ischemic insult.
Publisher: Wiley
Date: 06-2001
DOI: 10.1046/J.1442-9071.2001.00403.X
Abstract: The mechanisms underlying the adaptive response for achromatic impulses seen on achromatic fields were investigated. Foveal thresholds were measured for a static probe-impulse under two conditions of adaptation. Thresholds were obtained under gain-cl ed conditions after observers had reached steady-state adaptation and with a probe-flash paradigm. It was found that thresholds isolated on steady-state fields cannot be modelled using a single mechanism. Likewise, the probe-flash condition failed to reflect the response of a single mechanism. Both threshold functions showed distinct breaks occurring at about the same field luminance (approximately 1.0 log cd/m2). Optimum data fits required the incorporation of two mechanisms implying the existence of independent processes mediating detection. Chromatic isolation confirmed that differential adaptation had been unmasked in the long- and medium-wavelength sensitive cone inputs to the achromatic channel.
Publisher: Informa UK Limited
Date: 11-1992
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2014
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 04-11-2014
Abstract: To consider the effect of chronic arterial hypertension on the susceptibility of the retina to acute IOP challenge. Anesthetized adult Long-Evans rats with normal (n = 5, receiving saline subcutaneously), chronic high blood pressure (BP) for 4 weeks (n = 15, Angiotensin II subcutaneously), and acute high BP for 1 hour (n = 10, Angiotensin II intravenously) underwent IOP elevation (10-120 mm Hg, 5 mm Hg steps each 3 minutes). During IOP elevation, retinal function and ocular blood flow were monitored with electroretinogram (ERG) and laser-Doppler flowmetry (LDF), respectively. Blood pressure was monitored via a femoral artery cannula. Electroretinogram and LDF responses are expressed as a percentage of baseline and compared between groups. The left ventricle and the aorta were dissected to assess the morphologic changes associated with chronic hypertension. Four weeks of hypertension (systolic BP 192 ± 4 mm Hg) produced cardiac hypertrophy and thickened aortic arterial walls compared with controls (systolic BP 112 ± 3 mm Hg). Retinal function was unaltered with chronic hypertension compared with normotensive animals. During acute IOP elevation, ERG and LDF were reduced in a dose-dependent manner in all BP groups. Both chronic and acute hypertension made the ERG and LDF less susceptible to IOP elevation. However, the degree of resistance to IOP elevation was greater in acute hypertension compared with chronic hypertension (P < 0.05). Acute BP elevation makes retinal function and blood flow less susceptible to IOP elevation. The reduced susceptibility afforded by improved ocular perfusion pressure is compromised after 4 weeks of chronic hypertension.
Publisher: Wiley
Date: 30-07-2007
DOI: 10.1002/CNE.21449
Abstract: We have characterized the vascular, neuronal, and glial changes in oxygen-induced retinopathy, a model of retinopathy of prematurity (ROP). Newborn Sprague-Dawley rats were exposed to either 80% +/- 2% oxygen to postnatal day P11 and then room air until P18 (ROP) or room air for the entire duration (controls). Retinal structure was examined under the light microscope and following postembedding immunocytochemistry in central, midperipheral, and peripheral regions. Müller cells were evaluated immunocytochemically with glial fibrillary acidic protein. The extent of vascularization was established histologically. ROP caused significant thinning of the inner cellular and plexiform layers, which became more pronounced in the peripheral inner nuclear layer of ROP animals (11.3% loss vs. 25.4% loss). Amacrine cell amino acid levels were particularly vulnerable in the peripheral retina bipolar cells showed similar but less prominent changes. Müller cells had elevated glutamine levels and were most gliotic in the periphery. The vasculature extended to peripheral retinal regions at P18 in controls but not in ROP rats. The most striking pattern of change was evident in the midperipheral "transition zone" of ROP animals. Areas close to blood vessels showed neurochemical properties that were similar to those of the central retina, indicating a local protective effect of the inner retinal blood supply. We find that ROP produces complex vascular, neural, and glial changes that relate to the proximity of inner retinal blood vessels.
Publisher: Cambridge University Press (CUP)
Date: 07-2001
DOI: 10.1017/S0952523801184105
Abstract: Retinal neurons are generated in overlapping growth spurts with ganglion cell and cone populations peaking sooner than rod and bipolar cell numbers. As such the functional development of the inner and outer retinal components and elements within these strata (rods vs. cones) may differ. We considered the postnatal development of the postreceptoral components of the ERG (P2, oscillatory potentials) in the guinea pig. ERGs were also evaluated across albino and pigmented strains in order to consider the role that pigmentation has for functional development. Electroretinograms were collected on postnatal days PD1 to PD60 ( n = 4–7 per time point). The postreceptoral P2 litude and implicit time was extracted (digital subtraction of modelled P3 and filtering, 0.5–49 Hz). Intensity–response relationships were described using Naka–Rushton functions whose parameters were compared using a nonparametric bootstrap. Oscillatory potentials (OPs) were extracted following signal conditioning and filtering to remove the a - and b -waves and were described using a Gabor function. OP response parameters were compared using repeated measures ANOVA. Postreceptoral P2 litudes mature soon after birth (PD10–PD12). Oscillatory potentials show a similar postnatal litude development (PD10–PD12) but a later maturation in timing (PD20) compared with the postreceptoral waveform. All components (P3, P2, and OPs) declined at the same relative rate with age after PD12. Albino animals gave larger, faster, and more sensitive waveforms at all ages but showed the same age-related trends as did pigmented animals. Early development of inner retinal synapses in guinea pigs may underlie the rapid postnatal maturation of their postreceptoral response. These appear to be constrained by the development of receptoral responses. All components declined at the same rate suggesting either a change in the photoreceptoral response or changes to ocular impedance with age.
Publisher: Wiley
Date: 1992
Publisher: MyJove Corporation
Date: 07-2016
DOI: 10.3791/54158
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 07-2006
DOI: 10.1167/IOVS.05-1493
Abstract: To examine photoreceptor function in diabetes in detail by evaluating photoreceptor light activation, deactivation of the photoresponse, and recovery of the photoreceptor after bleaching (dark adaptation) in rats made diabetic with streptozotocin (STZ). Animals were assigned to treated and control groups. Light activation in rod photoreceptors was established using a paired-flash electroretinogram (ERG) protocol, and the leading edge of the a-wave was modeled with the mechanisms mediating phototransduction. Deactivation of the photoreceptor response was evaluated at three luminous exposures (1.4-2.2 log cd.m/s-2) using a variable interstimulus interval (ISI) paradigm. Dark adaptation was evaluated at 90-second intervals for 30 minutes after approximately 20% pigment bleach. At each time point, a paired-flash signal (1.4 log cd.s/m-2) was used to extract rod responses. Diabetic animals showed decreased litudes of the photoreceptor response 12 weeks after diabetes induction. No difference was found in the rate of deactivation of the photoresponse in diabetic rats. Normalized litudes showed that diabetic animals had significantly faster dark adaptation (P<0.01) than did controls. Although photoreceptor activation was abnormal, deactivation was unaltered after 12 weeks of diabetes. The faster relative recovery found in diabetes after bleach, in the presence of normal pigment dynamics, may reflect a decrease in outer segment lengths.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2008
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 12-10-2016
Abstract: To assess whether tear hyperosmolarity, being diagnostic of dry eye disease (DED), is associated with specific alterations to the cytokine content of human tears that may provide a biomarker for DED. In this prospective, cross-sectional, clinical study, participants (n = 77) were recruited from a single clinical site and categorized into groups based upon tear osmolarity status (n = 62 hyperosmolar, n = 15 normo-osmolar). Comprehensive anterior eye clinical assessments were undertaken. Concentrations of seven cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, and TNF-α) in basal tears were assayed using multiplex cytometric bead array. The main outcome measure was difference in cytokine concentration between groups. Group comparisons were undertaken using 2-tailed t-tests. Cohen's effect size was calculated for each finding. Spearman correlations between cytokine concentrations, clinical symptoms, and clinical parameters of DED were calculated. Tear hyperosmolarity was specifically associated with increased tear IFN-γ levels (13.3 ± 2.0 vs. 4.4 ± 1.4 pg/mL, P = 0.03). Cohen's effect size was large (0.8) for changes to tear IFN-γ levels. Significant correlations were observed between IFN-γ concentration and each of: tear osmolarity (r = 0.34 P = 0.007), total ocular surface staining (r = 0.56, P < 0.0001), and Schirmer test score (r = -0.33, P = 0.003). Tear hyperosmolarity is specifically associated with higher levels of the proinflammatory cytokine IFN-γ, which correlate with key clinical parameters of DED. The calculated effect size (0.8) suggests that this assay has diagnostic power as a biomarker for evaporative DED.
Publisher: SAGE Publications
Date: 22-08-2014
Abstract: In between migraine attacks, some people show visual field defects that are worse when measured closer to the end of a migraine event. In this cohort study, we consider whether electrophysiological responses correlate with visual field performance at different times post-migraine, and explore evidence for cortical versus retinal origin. Twenty-six non-headache controls and 17 people with migraine performed three types of perimetry (static, flicker and blue-on-yellow) to assess different aspects of visual function at two visits conducted at different durations post-migraine. On the same days, the pattern electroretinogram (PERG) and visual evoked response (PVER) were recorded. Migraine participants showed persistent, interictal, localised visual field loss, with greater deficits at the visit nearer to migraine offset. Spatial patterns of visual field defect consistent with retinal and cortical dysfunction were identified. The PERG was normal, whereas the PVER abnormality found did not change with time post-migraine and did not correlate with abnormal visual field performance. Dysfunction on clinical tests of vision is common in between migraine attacks however, the nature of the defect varies between in iduals and can change with time. People with migraine show markers of both retinal and/or cortical dysfunction. Abnormal visual field sensitivity does not predict abnormality on electrophysiological testing.
Publisher: Informa UK Limited
Date: 1991
Publisher: Wiley
Date: 28-04-2008
DOI: 10.1002/GLIA.20680
Abstract: We investigated the effect of receptor blockade induced by an angiotensin II type-1 receptor antagonist (AT(1)-RB) on glial and vascular changes in oxygen-induced retinopathy (OIR), a model of retinopathy of prematurity (ROP). OIR was induced in Sprague-Dawley rats by exposure to 80% oxygen from postnatal (P) days 0-11, followed by 7 days in room air. Control animals were in room air for the entire duration. One cohort of OIR and control pups received the AT(1)-RB valsartan (40 mg/kg/day intraperitoneal) from P11 to P18. The vascular response was examined immunocytochemically using retinal wholemounts and vertical sections labeled with endothelial (Isolectin-B4) and pericyte (NG2, desmin) markers. Glial cell changes were assessed by measuring cell numbers and immunoreactivity (S100beta, connexin-26, and glial fibrillary acidic protein). OIR resulted in extensive intravitreal neovascularization and under-development of the outer vascular plexus. Pericyte numbers were not significantly affected in OIR, although pericyte-endothelial (desmin-IB4) interactions were impaired. Peripheral astrocyte degeneration occurred between P11 and P13 with prominent Müller cell reactivity at P18. Valsartan imparted a protective effect on glia and blood vessels in OIR. At P18, valsartan-treated OIR retinae showed significantly greater astrocyte survival, improved revascularization of the retina, and reduced preretinal neovascularization and Müller cell reactivity. This study identifies a glio-vascular protective effect with AT(1)-RB in OIR.
Publisher: Springer Science and Business Media LLC
Date: 1998
Abstract: This study considers the precision and accuracy of bipolar corneal electrodes compared with unipolar intravitreal methods in collecting electroretinographic (ERG) recordings from a small animal. Flash ERGs were obtained from 9 adult guinea pigs on three occasions. Corneal bipolar (Burian-Allen) electrodes were used to collect data on the first two occasions whereas unipolar intravitreal electrodes were used on the last. We identified the a-wave, b-wave, oscillatory potentials, PIII and PII responses. Intensity-response functions were fit using a Naka-Rushton relationship with a bootstrap estimating the 95% confidence limits. Discrepancy analysis was applied to determine the coefficient of agreement. We found significantly larger litudes with unipolar intravitreal electrodes (ANOVA a-wave, p<0.002 b-wave, p<0.001 Oscillatory potentials (OPs), p<0.005) especially at high intensities. Implicit times showed little differences between electrodes for the a-wave, significantly faster (p<0.03) b-waves at some intensities, and significantly slower (p O.05) if expressed in logarithmic units but PII litude (log microV) was significantly smaller with corneal electrodes. We suggest that a conversion factor (x1.35) should be applied to data collected with bipolar corneal electrodes to estimate the litudes of the modelled parameters accurately. The corneal electrode gave a precision of +/-39 microV which yields a statistical power of 0.90 for a s le size of 7 subjects. We conclude that bipolar corneal electrodes provide smaller electroretinogram litudes due to their location and reduced span of the retinal generators.
Publisher: Mary Ann Liebert Inc
Date: 12-1994
Abstract: We describe a highly efficient calcium phosphate transfection protocol capable of achieving 100% transfection efficiency of reporter genes transiently expressed in the human hepatoma cell lines HuH7 and HepG2. This procedure, a modification of that described by Chen and Okayama, is reliable, reproducible, and eliminates the requirement for the inclusion of cotransfected internal control plasmids. While Chen and Okayama described the pH of the 2x BBS (N,N-bis[2-hydroxyethyl]-2-aminoethanesulfonic acid-buffered saline) and DNA concentration as being critical factors for optimal transfection efficiency, we show that a reduced and strictly monitored standing time of the DNA/CaCl2/2x BBS cocktail prior to addition to cultured cells is essential for a particular combination of pH and DNA concentration. We also show that the inclusion of internal control plasmids can inhibit reporter gene activity in a promoter- and dose-dependent manner. The method so described is also applicable for the transfection of other mammalian cell lines including COS and HeLa, and conceivably for the generation of stable transfectants at high frequency.
Publisher: Wiley
Date: 07-2002
DOI: 10.1046/J.1475-1313.2002.00036.X
Abstract: To evaluate and compare the functional and perceived benefits of wearing coloured lenses by patients with age-related macular degeneration (ARMD). Ten subjects with early ARMD and five elderly controls wore a selection of NoIR wrap-around coloured lenses (yellow 29.7% light transmission, orange 22.9%, red 16.8% and grey 10.3%), each for a duration of 7 days. Contrast sensitivity, colour vision, visual acuity, the effect of glare and peripheral sensitivity were measured for each lens and compared with a control (no lens) condition. Subjective ratings of visual performance were also scored. Compared with the no filter condition, red and grey lenses reduced contrast sensitivity whereas yellow and orange lenses increased contrast sensitivity. These objective changes were supported by subjective ratings in subjects with ARMD. Grey lenses reduced the loss of contrast sensitivity usually suffered in the presence of glare, whereas visual acuity and peripheral sensitivity decreased with red lenses. Colour vision became distorted with red lenses in control subjects, but was relatively unaffected by the use of coloured lenses in subjects with ARMD. The subjective benefit of coloured lenses appears to be due to a minor enhancement of contrast sensitivity.
Publisher: Wiley
Date: 08-2015
DOI: 10.14814/PHY2.12507
Publisher: Informa UK Limited
Date: 03-2004
Publisher: Springer Science and Business Media LLC
Date: 06-2011
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.AJO.2018.03.009
Abstract: To establish the medium-term repeatability of the iPad perimetry app Melbourne Rapid Fields (MRF) compared to Humphrey Field Analyzer (HFA) 24-2 SITA-standard and SITA-fast programs. Multicenter longitudinal observational clinical study. Sixty patients (stable glaucoma/ocular hypertension/glaucoma suspects) were recruited into a 6-month longitudinal clinical study with visits planned at baseline and at 2, 4, and 6 months. At each visit patients undertook visual field assessment using the MRF perimetry application and either HFA SITA-fast (n = 21) or SITA-standard (n = 39). The primary outcome measure was the association and repeatability of mean deviation (MD) for the MRF and HFA tests. Secondary measures were the point-wise threshold and repeatability for each test, as well as test time. MRF was similar to SITA-fast in speed and significantly faster than SITA-standard (MRF 4.6 ± 0.1 minutes vs SITA-fast 4.3 ± 0.2 minutes vs SITA-standard 6.2 ± 0.1 minutes, P < .001). Intraclass correlation coefficients (ICC) between MRF and SITA-fast for MD at the 4 visits ranged from 0.71 to 0.88. ICC values between MRF and SITA-standard for MD ranged from 0.81 to 0.90. Repeatability of MRF MD outcomes was excellent, with ICC for baseline and the 6-month visit being 0.98 (95% confidence interval: 0.96-0.99). In comparison, ICC at 6-month retest for SITA-fast was 0.95 and SITA-standard 0.93. Fewer points changed with the MRF, although for those that did, the MRF gave greater point-wise variability than did the SITA tests. MRF correlated strongly with HFA across 4 visits over a 6-month period, and has good test-retest reliability. MRF is suitable for monitoring visual fields in settings where conventional perimetry is not readily accessible.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 09-12-2011
DOI: 10.1167/IOVS.10-7043
Abstract: To evaluate the potential of psychophysical assessments of retinal function to provide diagnostic biomarkers of early age-related macular degeneration (AMD). Unilateral visual function was assessed in 221 participants (72.86 ± 9.94 years 67% women) with early AMD (visual acuity better than 20/60) and 109 controls (73.07 ± 10.32 years 65% women). Psychophysical assessment included steady state thresholds (4- and 14-Hz flicker and red and blue color) and dynamic tests (photostress recovery [PSR] and dark adaptation [DA]). All test parameters were compared in terms of their diagnostic capacity (sensitivity and specificity), reproducibility, and clinical applicability (test duration and participant's perception of test difficulty). AMD status was determined by digital photography, according to the International Classification and Grading System. All functional measurements were significantly worse, on average, in the AMD group than in the control group (P < 0.001). Static and dynamic parameters showed weak correlations (range, 0.003-0.225). Rod recovery in DA and cone recovery in PSR had the best diagnostic capacity (area under curve [AUC], receiver operating characteristic [ROC] analysis, 0.93 ± 0.016 and 0.85 ± 0.021, respectively). Considering diagnostic capacity together with test reproducibility and clinical applicability, the 14-Hz flicker gave the best outcome, followed by PSR. Combination of these two tests detected 71% of abnormal early AMD cases. All the visual function tests had good diagnostic capacity. Combination of the 14-Hz flicker thresholds and dynamics of the PSR test provided optimal quantitative assessment of retinal function in early AMD, suggesting that this set is a potentially useful clinical tool for following progression of early AMD and assessing the efficacy of interventions.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2013
Publisher: Optica Publishing Group
Date: 20-07-1994
DOI: 10.1364/AO.33.004741
Publisher: Informa UK Limited
Date: 11-2007
DOI: 10.1111/J.1444-0938.2007.00179.X
Abstract: This report describes the short- and long-term ocular signs and symptoms of a patient with an orbital blow-out fracture and discusses the differential diagnosis of vertical diplopia. A blow-out fracture occurs when blunt trauma is applied either directly to the eyeball itself or the orbital rim and usually results in a fracture of the orbital floor with consequential excavation and entrapment of orbital contents in the fracture. Vertical diplopia is a common presenting symptom for a blow-out fracture of the orbit but careful considerations should be given to other potential conditions leading to such diplopia. A patient is presented who suffered a blow-out fracture almost a decade earlier, secondary to blunt trauma to the globe. The clinical findings are provided immediately after the trauma, post-surgery and during a recent ocular examination.
Publisher: Elsevier BV
Date: 09-2007
DOI: 10.1016/J.VISRES.2007.05.005
Abstract: Symmetric flicker modulates about a background light level and effects no change in the time-average luminance. Rectified flicker is achieved by modulating a luminance-increment and results in both a flickering component and an increase in the time-averaged luminance (luminance-pedestal) above the adapting background light level. We studied the effect that changes in adapting light level and local luminance (within the area of the flickering target) have on thresholds. We measured thresholds for single and multiple cycles of flicker over a range of adapting light levels (Threshold versus Intensity paradigm) and defined their gain as a function of luminance-pedestal litude (Threshold versus Amplitude paradigm). The dynamics of symmetric and rectified flicker responses were determined using a Stimulus Onset Asynchrony paradigm. The data show rectified flicker thresholds differ from symmetric flicker thresholds due to two factors that can be contrast-dependent or contrast-independent: (1) local adaptation, which varies with stimulus duration and (2) surround interactions that depend on adapting light level. The dynamics of the thresholds for symmetric and rectified flicker stimuli suggest the detection mechanisms occur early in the visual pathways, involving the magnocellular pathway.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 04-09-0009
DOI: 10.1167/IOVS.09-3814
Abstract: To examine retinal function using the full-field electroretinogram (ERG) during and after acute intraocular pressure (IOP) elevation in wild-type mice. IOP was elevated by anterior chamber cannulation in wild-type C57/BL6 mice. The pressure-function relationship was determined by IOP elevation in steps from baseline to 80 mm Hg. The rate of functional recovery was assessed for 60 minutes after an IOP spike of 50 mm Hg for 30 minutes. During and immediately after IOP elevation, scotopic ERG signals were recorded in response to dim and bright flashes (-4.54, -2.23, and 0.34 log cd x s x m(-2)) and analyzed for photoreceptoral (a-wave), ON-bipolar (b-wave), oscillatory potentials (OPs), and scotopic threshold responses (positive [p]STR/negative [n] STR). A full ERG protocol was collected 2 days before and 7 days after the single 50-mm Hg IOP spike. The pSTR was most sensitive to IOP elevation with 50% litude loss (mu) at 41 mm Hg (mu, 95% confidence limits (CL): 37.7, 45.6) followed by nSTR at 45 mm Hg (95% CL: 41.0, 49.1). pSTR was significantly more sensitive than the b-wave (95% CL: 41.4, 49.1), a-wave (95% CL: 47.6, 55.3), and OPs (95% CL: 49.6, 59.2). pSTR showed slower recovery immediately after the 50 mm Hg spike compared with the b-wave (P = 0.02). One week after the 50-mm Hg spike, pSTR (-30% +/- 6%, P < 0.001) and OP (-27% +/- 2%, P < 0.001) litudes were reduced, whereas other components were unaffected. The STR in mice is more sensitive to acute IOP elevation and recovers slower than other ERG components. Reduction in pSTR and OP litude at 1 week suggests persistent impairment of inner retinal function can occur after a single IOP spike.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-1994
DOI: 10.1097/00006324-199408000-00004
Abstract: We report two experiments that address the role of stereopsis in viewing the fundus. Thirteen observers viewed stereo slides obtained by lateral displacement of a fundus camera. We quantified the capacity of seven clinicians (normal stereopsis) to resolve depth in a model eye viewed monocularly and binocularly. We also compared the ability of the same seven and six additional clinicians (with reduced stereopsis) to determine the relative position of the cup shown in normal and reverse disparity as well as answering a questionnaire. We determined optimal performance based on a schematic eye. Monocular viewing gives better than expected results with binocularity being of greatest benefit for small disparities. Clinicians perform much worse in stereoscopic judgments than predicted by calculation. Few clinicians report making stereo depth judgments in practice. All amblyopic observers report using hyperacuity cues. This study shows that binocularity and stereopsis are beneficial for judging small disparities under limited circumstances. The level of stereopsis achieved in practice fails to approach the expected limit. We believe that this constriction arises from a known limit to stereo acuity associated with extended fields.
Publisher: Informa UK Limited
Date: 11-1992
Safety and Efficacy of a Preservative-Free Artificial Tear Containing Carboxymethylcellulose and Hyaluronic Acid for Dry Eye Disease: A Randomized, Controlled, Multicenter 3-Month Study
Publisher: Informa UK Limited
Date: 10-2020
DOI: 10.2147/OPTH.S256480
Publisher: Wiley
Date: 06-2000
DOI: 10.1046/J.1442-9071.2000.00299.X
Abstract: We investigated the relationship between stimulus duration and flicker thresholds when flickering stimuli were presented on luminance pedestals. Mean-modulated flicker thresholds remained constant with changes in stimulus duration. However, flicker presented on a luminance pedestal gave masking at short durations, decaying exponentially to stable thresholds with time. These stable thresholds were elevated when compared with the mean-modulated condition. The lowest threshold in a stimulus onset asynchrony function predicted the threshold obtained from a luminance-pedestal flicker stimulus of the same duration. This suggests that luminance-pedestal flicker thresholds are determined by the most detectable cycle in a multiple cycle stimulus. We find that the 800 ms stimulus duration used in the Medmont M600 perimeter (Medmont, Camberwell, Australia) is suitable to determine stable flicker thresholds.
Publisher: Elsevier BV
Date: 06-2009
DOI: 10.1016/J.EXER.2009.01.009
Abstract: The aim of this study was to determine whether inner retinal dysfunction in diabetic rats is correlated with structural and/or biochemical changes in the retina and optic nerve. Using the electroretinogram (ERG -5.83 to 1.28 log cd.s.m(-2)) retinal function (photoreceptor, bipolar, amacrine and ganglion cell components) was measured in control (n=13 citrate buffer) and diabetic (n=13 streptozotocin, STZ, 50 mg kg(-1)) rats, 12 weeks following treatment. Retinae and optic nerves were analyzed for structural changes and retinae were assessed for alterations in growth factor/cytokine expression using quantitative real-time PCR. We found that phototransduction efficiency was reduced 12 weeks after STZ-induced diabetes (-30%), leading to reduced litude of ON-bipolar (-18%) and amacrine cell (-29%) dominated responses ganglion cell dysfunction (-84%) was more profound. In the optic nerve, nerve fascicle area and myelin sheath thickness were reduced (p<0.05), whereas the ratio of blood vessels and connective tissue to total nerve cross-sectional area was increased (p<0.05) in diabetic compared to control rats. In the retina, connective tissue growth factor (CTGF), transforming growth factor beta, type 2 receptor (TGFbeta-r2) mRNA and platelet-derived growth factor B (PDGF-B) mRNA were increased (p<0.035). Reduced ganglion cell function was correlated with increased CTGF and TGFbeta-r2, but not PDGF-B mRNA. In summary, the ganglion cell component exhibited the greatest level of dysfunction within the ERG components examined after 12 weeks of STZ-induced diabetes the level correlated with increased CTGF and TGFbeta-r2 mRNA, but not with gross morphological changes in the retina or optic nerve.
Publisher: Wiley
Date: 06-2001
DOI: 10.1046/J.1442-9071.2001.00402.X
Abstract: The contribution of rods and cones to the scotopic electroretinogram (ERG) of small animals is unclear, with a recent report suggesting that the mouse has no cone a-wave. The present study considered the contribution of cones to the ERG of the rat. Dark-adapted Long Evans rats (n = 4) had ERG signals collected following a single flash, which stimulated rods and cones (mixed response), or a twin-fash paradigm (short interstimulus interval, 1 s), which isolated cone responses. Rod signals were derived by digital subtraction of the cone signal from the mixed rod/cone ERG. The rat a-wave was found to be dominated by rod responses but cone responses contributed substantially (45%) to post-receptoral waveforms (b-wave) at higher light levels.
Publisher: MDPI AG
Date: 27-03-2023
DOI: 10.3390/JCM12072530
Abstract: Background: To determine the 12-month compliance with and retention of home monitoring (HM) with Melbourne Rapid Fields (MRFh) for patients with intermediate age-related macular degeneration (iAMD) and compare visual acuity (VA) and retinal sensitivity (RS) results to clinical measures. Methods: Participants were recruited to a 12-month HM study with weekly testing of vision with MRFh. Inclusion criteria were a diagnosis of iAMD, understand English instructions, VA ≥ 20/40, and access to an iPad. Supervised in-clinic testing of high contrast VA (HVA, ETDRS), low-luminance VA (LLVA, ETDRS with ND2 filter), and RS (Macular Integrity Assessment, MAIA, and MRF in-clinic, MRFc) was conducted every 6-months. Results: A total of 54 participants (67 ± 6.8 years) were enrolled. Compliance to weekly HM was 61% and study retention at 12-months was 50% of those with uptake (n = 46). No difference was observed between MRFc and MRFh across all RS and VA outcomes (p 0.05). MRFh RS was higher than MAIA (29.1 vs. 27.1 dB, p 0.001). MRFh HVA was not different from ETDRS (p = 0.08), but LLVA was 9 letters better (81.5 vs. 72.4 letters, p 0.001). Conclusions: Over 12-months, MRFh yields a moderate level of compliance with (61%) and retention (50%) of weekly testing. Further studies are required to assess the ability of MRFh to detect early progression to nAMD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-1994
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 03-2010
DOI: 10.1167/IOVS.09-3792
Abstract: Diabetes results in an insulin-related disorder of lipid metabolism that reduces production of long-chain polyunsaturated fatty acids (PUFAs e.g., docosahexanoic acid, DHA). This study considers the role that this lipid change has on retinal function. From conception, rats (n = 56) were fed diets either balanced (n = 32) in PUFAs or deficient in omega-3 (n = 24). Half were assigned to control (n = 28) or streptozotocin (STZ: n = 28) treatment at 7 weeks of age. Key metabolic indices were assayed at 19 weeks, and retinal function was determined by electroretinogram (ERG) at 20 weeks. Retinal anatomy and lipid assays of 20-week-old animals were used to identify structural changes and tissue PUFA content. The systemic indices of diabetic rats were not affected by diet. Lipid composition of retinal membranes reflected the dietary manipulation, and diabetes lified some fatty acid changes consistent with reduced desaturase activity. Diabetes produced significant reduction in rod function (-33%) only in the absence of fish oil, whereas cone responses (-46%) and inner retinal oscillatory potentials (-47%) showed either no effect of diet or a partial diet effect with a significant diabetes effect. Anatomic analysis revealed no disorder in the retinal neurons, although changes in the Müller glia were noted in diabetes, regardless of diet. A diet balanced in long-chain PUFAs modifies retinal lipid membranes in diabetes and prevents rod dysfunction. Dietary modification was not found in the cone or glial response but a partial improvement was evident in the OPs, most likely secondary to the larger photoreceptor output.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 09-2004
DOI: 10.1167/IOVS.04-0253
Publisher: Elsevier BV
Date: 11-2001
Publisher: Public Library of Science (PLoS)
Date: 12-09-2013
Publisher: Informa UK Limited
Date: 07-1995
Publisher: Elsevier BV
Date: 2005
Publisher: American Medical Association (AMA)
Date: 12-2015
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.PRETEYERES.2015.07.006
Abstract: Migraine is a common and debilitating primary headache disorder that affects 10-15% of the general population, particularly people of working age. Migraine is relevant to providers of clinical eye-care because migraine attacks are associated with a range of visual sensory symptoms, and because of growing evidence that the results of standard tests of visual function necessary for the diagnosis and monitoring of glaucoma (visual fields, electrophysiology, ocular imaging) can be abnormal due to migraine. These abnormalities are measureable in-between migraine events (the interictal period), despite patients being asymptomatic and otherwise healthy. This picture is further complicated by epidemiological data that suggests an increased prevalence of migraine in patients with glaucoma, particularly in patients with normal tension glaucoma. We discuss how migraine, as a co-morbidity, can confound the results and interpretation of clinical tests that form part of contemporary glaucoma evaluation, and provide practical evidence-based recommendations for the clinical testing and management of patients with migraine who attend eye-care settings.
Publisher: Elsevier BV
Date: 04-1998
DOI: 10.1016/S0042-6989(97)00250-2
Abstract: We investigated the nature of color and luminance processes under threshold and suprathreshold conditions in normal trichromatic observers. Detection and discrimination contours as well as threshold-vs-contrast (Tvc) functions were measured in the Derrington-Krauskopf-Lennie (DKL) color space using a masking paradigm. Such contours revealed substantial threshold asymmetries along the three cardinal axes for excursions of opposite polarity along a single axis (e.g. "red" vs "green"). The detection threshold asymmetry was significant for the "blue" and "yellow" (P < 0.05) and luminance increments and decrements (P < 0.01). For suprathreshold discrimination contours the polarity of these asymmetries reversed but remained significant for "blue" and "yellow" (P < 0.001) and luminance increments and decrements (P < 0.01). No significant differences were found between the "red" and "green" cardinal axes under either condition. The discrimination contours also indicated that suprathreshold performance had variable masking along the different axes. A characteristic Tvc curve was found in all cardinal directions except "yellow". The Tvc for "yellow" differed from the other cardinal directions by showing no masking after the initial facilitation and by giving a greater saturating response as a function of contrast. We considered whether the state of retinal adaptation had any role in producing the asymmetries.
Publisher: Wiley
Date: 29-08-2007
DOI: 10.1002/CNE.21470
Abstract: Studies of retinal ischemia/reperfusion indicate a disparity between the anatomical and functional results while a large number of rod bipolar cells remain postischemia, there is a significant reduction in the litude of the scotopic b-wave of the electroretinogram (ERG). We investigated the alterations in photoreceptor-bipolar cell signaling following ischemia/reperfusion and suggest a mechanism for the decrease in b-wave litude. A cation channel probe (agmatine, 1-amino-4-guanidobutane, AGB) was used to assess cellular ion channel activity in neurochemically identified cells secondary to endogenous glutamate release or pharmacological manipulations. By applying the "neurochemical truth point" principle (Sun et al. [2007a] J Comp Neurol, this issue), we have been able to confirm the loss of specific subpopulations of neurons. ERG was used to assess gross retinal function, with parameters of the ERG model providing insight into changes in the phototransduction cascade and sensitivity of postreceptoral glutamate receptors. Following ischemia/reperfusion, rod bipolar cells maintained 2-amino-4-phosphonobutyric acid-responsive metabotropic glutamate receptors and displayed no change in sensitivity to flashes of light as assessed by ERG. Therefore, the loss in b-wave litude is likely due to alterations in photoreceptoral glutamate release detected as a change in postsynaptic AGB permeation into rod bipolar cells. Bipolar cell to amacrine cell signaling was also altered. The robust AGB entry into cholinergic amacrine cells was virtually absent in retinas that had undergone ischemia/reperfusion but remained in the AII amacrine cells. Such results suggest a loss of glutamate receptors and/or a change in receptor subunit expression in subpopulations of inner retinal neurons. Although many cells retain their characteristic neurochemical labeling following ischemia/reperfusion, caution should be used when assuming cells participate in functional retinal circuits based solely on the persistence of neurochemical labeling.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2013
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 06-2003
DOI: 10.1167/IOVS.02-1054
Abstract: To consider how aerobic and anaerobic metabolic processes limit posthypoxemic decay in retinal function, measured by electroretinogram (ERG). The hypothesis that lowering metabolic demand would prolong endogenous metabolic stores was tested by comparing the rate of ERG decay in rats in dark- (n = 5) versus light-adapted (15 minutes, 112 cd/m(2), n = 5) conditions and with serial versus single (n = 5 at each of seven time points) light stimulation. Postmortem hypoxemia was induced by cervical dislocation. Glucose (10 and 100 mM) and glutamine or lactate (100 mM) were injected into the vitreous 10 minutes before hypoxemic insult, to consider glycolytic-oxidative versus oxidative metabolism, respectively. Lowering the metabolic drain by light adaptation or serial stimulation significantly improved the photoreceptoral saturated litude during the first 5 to 7.5 minutes after postmortem hypoxemia. Increasing substrate availability with exogenous glucose preloading delayed the loss of the photoreceptoral response, thereby extending the delay constant from 4.8 to 10.9 minutes. Postreceptoral litudes were not improved by any exogenous substrate. Providing glucose at 5 minutes after hypoxemia provided no benefits. Similar to glucose, glutamine and lactate loading significantly delayed photoreceptoral decay over the first 7.5 minutes, after which time glucose was the more effective substrate. The postmortem decay of photoreceptoral function reflects depletion of both endogenous oxygen and carbon substrate reserves. The findings provide evidence that a transition between aerobic and anaerobic metabolism occurs after approximately 8 minutes of complete hypoxemia.
Publisher: Informa UK Limited
Date: 03-1994
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-1998
DOI: 10.1097/00006324-199807000-00020
Abstract: To ascertain the accuracy and precision of the catch-trial monitor used to estimate the false-response rate in automated perimetry. False responses were automatically injected at various rates by modified perimetric software while reliable perimetric subjects underwent visual field thresholding. Four repeat tests were conducted within a 1-hour period to quantify the variability and bias inherent in the catch-trial technique. The catch-trial method gave a very accurate estimate of the average false-response rate. Precision, however, was quite poor because of the small s le of catch trials. Outcomes were predicted using a binomial model, and we demonstrated good concordance between the model and empirical data. When the true false-response rate was 33%, estimates derived from catch trials ranged from 7 to 57%. Although the catch-trial method gave an accurate estimate of the false-response rate, confidence intervals were too wide to provide a high level of precision. Our data suggest that tests with reported false-response rates < 20% may be considered reliable.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2014
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 07-08-2012
DOI: 10.1167/IOVS.11-8958
Abstract: The aim of this study was to investigate the relationship between clinical macular changes and retinal function in age-related macular degeneration (AMD). We recruited 357 participants with visual acuity of better than 20/60 in the study eye, including 64 in iduals with normal fundi and 293 AMD participants classified into 12 subgroups based upon the International Classification and Grading System. Visual function in the study eye was assessed using two steady-state tests (achromatic 14 Hz flicker [F14Hz] and isoluminant blue color [BCT]) and two adaptation measurements (cone photo-stress recovery rate [CRR] and rod dark adaptation recovery rate [RRR]). The groups were compared on their average psychophysical measurements and ranked according to functional deficiency. Both adaptation parameters were significantly abnormal when only hard and/or intermediate drusen were evident (compared to controls, P < 0.023) and yielded considerably worse outcomes in cases with more advanced fundus changes (P < 0.001), but provided limited ability to discriminate between these cases (linear trend, CRR t = 0.68, P = 0.50 and RRR t = 1.76, P = 0.08). Steady-state measurements, however, declined gradually along the entire hierarchy of fundus changes (linear trend, F14Hz t = 10.16, P < 0.001 and BCT t = 11.19, P < 0.001) with F14Hz being able to detect significant functional change as early as in the intermediate drusen group, when compared to controls (P = 0.003). Steady state thresholds (F14Hz and BCT) and clinical signs showed significant concordance across the spectrum of early AMD fundus changes. This suggests that these tests may be an effective tool for monitoring progression of AMD to supplement clinical grading.
Publisher: Hindawi Limited
Date: 2016
DOI: 10.1155/2016/5801826
Abstract: Objective . To examine whether retinal electrophysiology is a useful surrogate marker of drug penetrance into the central nervous system (CNS). Materials and Methods . Brain and retinal electrophysiology were assessed with full-field visually evoked potentials and electroretinograms in conscious and anaesthetised rats following systemic or local administrations of centrally penetrant (muscimol) or nonpenetrant (isoguvacine) compounds. Results . Local injections into the eye/brain bypassed the blood neural barriers and produced changes in retinal/brain responses for both drugs. In conscious animals, systemic administration of muscimol resulted in retinal and brain biopotential changes, whereas systemic delivery of isoguvacine did not. General anaesthesia confounded these outcomes. Conclusions . Retinal electrophysiology, when recorded in conscious animals, shows promise as a viable biomarker of drug penetration into the CNS. In contrast, when conducted under anaesthetised conditions confounds can be induced in both cortical and retinal electrophysiological recordings.
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.PHARMTHERA.2017.02.009
Abstract: The retina is an easily accessible out-pouching of the central nervous system (CNS) and thus lends itself to being a biomarker of the brain. More specifically, the presence of neuronal, vascular and blood-neural barrier parallels in the eye and brain coupled with fast and inexpensive methods to quantify retinal changes make ocular biomarkers an attractive option. This includes its utility as a biomarker for a number of cerebrovascular diseases as well as a drug pharmacology and safety biomarker for the CNS. It is a rapidly emerging field, with some areas well established, such as stroke risk and multiple sclerosis, whereas others are still in development (Alzheimer's, Parkinson's, psychological disease and cortical diabetic dysfunction). The current applications and future potential of retinal biomarkers, including potential ways to improve their sensitivity and specificity are discussed. This review summarises the existing literature and provides a perspective on the strength of current retinal biomarkers and their future potential.
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/796362
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.OPHTHA.2016.09.023
Abstract: To assess the efficacy of 2 forms of oral long-chain omega-3 (ω-3) essential fatty acid (EFA) supplements, phospholipid (krill oil) and triacylglyceride (fish oil), for treating dry eye disease (DED). Randomized, double-masked, placebo-controlled clinical trial. This study was conducted at a single site and involved 60 participants with mild to moderate DED who were randomized (1:1:1) to 1 of 3 groups: placebo (olive oil), krill oil, or fish oil supplements. Participants received 1 of the 3 interventions: placebo (olive oil 1500 mg/day), krill oil (945 mg/day eicosapentaenoic acid [EPA], + 510 mg/day docosahexaenoic acid [DHA]), or fish oil (1000 mg/day EPA + 500 mg/day DHA) for 90 days, with monthly study visits. Primary outcome measures were mean change in (1) tear osmolarity and (2) DED symptoms (Ocular Surface Disease Index [OSDI] score) between days 1 and 90. Secondary outcomes included mean change in key clinical signs (tear stability, tear production, ocular surface staining, bulbar and limbal redness, tear volume, anterior blepharitis, meibomian gland capping) and tear inflammatory cytokine levels. In total, 54 participants completed the study. At day 90, tear osmolarity was reduced from baseline with both krill oil (mean ± standard error of the mean: -18.6±4.5 mOsmol/l n = 18 P < 0.001) and fish oil (-19.8±3.9 mOsmol/l n = 19 P < 0.001) supplements, compared with placebo (-1.5±4.4 mOsmol/l n = 17). OSDI score was significantly reduced at day 90 relative to baseline in the krill oil group only, compared with placebo (-18.6±2.4 vs. -10.5±3.3 P = 0.02). At day 90, there were also relative improvements in tear breakup time and ocular bulbar redness, compared with placebo, for both forms of ω-3 EFAs. Basal tear levels of the proinflammatory cytokine interleukin 17A were significantly reduced in the krill oil group, compared with placebo, at day 90 (-27.1±10.9 vs. 46.5±30.4 pg/ml P = 0.02). A moderate daily dose of both forms of long-chain ω-3 EFAs, for 3 months, resulted in reduced tear osmolarity and increased tear stability in people with DED. Omega-3 EFAs in a predominantly phospholipid form (krill oil) may confer additional therapeutic benefit, with improvements in DED symptoms and lower basal tear levels of interleukin 17A, relative to placebo.
Publisher: Elsevier BV
Date: 02-2009
DOI: 10.1016/J.OPHTHA.2008.09.002
Abstract: To elucidate the contribution of environmental versus genetic factors to the significant losses in visual function associated with normal aging. A classical twin study. Forty-two twin pairs (21 monozygotic and 21 dizygotic age 57-75 years) with normal visual acuity recruited through the Australian Twin Registry. Cone function was evaluated by establishing absolute cone contrast thresholds to flicker (4 and 14 Hz) and isoluminant red and blue colors under steady state adaptation. Adaptation dynamics were determined for both cones and rods. Bootstrap res ling was used to return robust intrapair correlations for each parameter. Psychophysical thresholds and adaptational time constants. The intrapair correlations for all color and flicker thresholds, as well as cone absolute threshold, were significantly higher in monozygotic compared with dizygotic twin pairs (P<0.05). Rod absolute thresholds (P = 0.28) and rod and cone recovery rate (P = 0.83 P = 0.79, respectively) did not show significant differences between monozygotic and dizygotic twins in their intrapair correlations, indicating that steady-state cone thresholds and flicker thresholds have a marked genetic contribution, in contrast with rod thresholds and adaptive processes, which are influenced more by environmental factors over a lifetime. Genes and the environment contribute differently to important neuronal processes in the retina and the role they may play in the decline in visual function as we age. Consequently, retinal structures involved in rod thresholds and adaptive processes may be responsive to appropriate environmental manipulation. Because the functions tested are commonly impaired in the early stages of age-related macular degeneration, which is known to have a multifactorial etiology, this study supports the view that pathogenic pathways early in the disease may be altered by appropriate environmental intervention. The authors have no proprietary or commercial interest in any materials discussed in this article.
Publisher: Informa UK Limited
Date: 12-11-1998
DOI: 10.1111/J.1444-0938.1998.TB06745.X
Abstract: BACKGROUND: Acute closure of the anterior chamber angle can have catastrophic consequences for vision when it occurs in an unsupervised situation. Visual debilitation is much less likely to result when angle-closure occurs in a well-controlled environment that allows appropriate management. Therefore, it is desirable for optometrists to undertake a complete ocular health assessment, including mydriatic fundus examination, on patients who have narrow anterior chamber angles, provided that appropriate precautions and procedures are followed. CASE REPORT: We report on the case of a 59-year-old white female whose anterior chamber angles closed in response to mydriatic drops instilled during an optometric examination. Her optic discs and visual field results from before and four years after the angle-closure attack do not show any significant changes. CONCLUSION: We conclude that the optimal standard of care for patients presenting to an optometric practice, and who are subsequently found to have narrow anterior chamber angles, includes pupillary dilatation to allow stereoscopic visualisation of the optic nerve head. Precautions must be followed to ensure that, in the unlikely event of an ensuing angle-closure episode, the attack occurs under clinically supervised conditions.
Publisher: MDPI AG
Date: 21-12-2020
DOI: 10.3390/COMPUTATION8040107
Abstract: The Lennard–Jones potential and a continuum approach can be used to successfully model interactions between various regular shaped molecules and nanostructures. For single atomic species molecules, the interaction can be approximated by assuming a uniform distribution of atoms over surfaces or volumes, which gives rise to a constant atomic density either over or throughout the molecule. However, for heterogeneous molecules, which comprise more than one type of atoms, the situation is more complicated. Thus far, two extended modeling approaches have been considered for heterogeneous molecules, namely a multi-surface semi-continuous model and a fully continuous model with average smearing of atomic contribution. In this paper, we propose yet another modeling approach using a single continuous surface, but replacing the atomic density and attractive and repulsive constants in the Lennard–Jones potential with functions, which depend on the heterogeneity across the molecules, and the new model is applied to study the adsorption of coronene onto a graphene sheet. Comparison of results is made between the new model and two other existing approaches as well as molecular dynamics simulations performed using the LAMMPS molecular dynamics simulator. We find that the new approach is superior to the other continuum models and provides excellent agreement with molecular dynamics simulations.
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/201726
Abstract: Age-related macular degeneration (AMD) is the leading cause of substantial and irreversible vision loss amongst elderly populations in industrialized countries. The advanced neovascular (or “wet”) form of the disease is responsible for severe and aggressive loss of central vision. Current treatments aim to seal off leaky blood vessels via laser therapy or to suppress vessel leakage and neovascular growth through intraocular injections of antibodies that target vascular endothelial growth factor (VEGF). However, the long-term success of anti-VEGF therapy can be h ered by limitations such as low or variable efficacy, high frequency of administration (usually monthly), potentially serious side effects, and, most importantly, loss of efficacy with prolonged treatment. Gene transfer of endogenous antiangiogenic proteins is an alternative approach that has the potential to provide long-term suppression of neovascularization and/or excessive vascular leakage in the eye. Preclinical studies of gene transfer in a large animal model have provided impressive preliminary results with a number of transgenes. In addition, a clinical trial in patients suffering from advanced neovascular AMD has provided proof-of-concept for successful gene transfer. In this mini review, we summarize current theories pertaining to the application of gene therapy for neovascular AMD and the potential benefits when used in conjunction with endogenous antiangiogenic proteins.
Publisher: Public Library of Science (PLoS)
Date: 03-11-2014
Publisher: Springer Science and Business Media LLC
Date: 08-09-2010
DOI: 10.1007/S10633-009-9193-6
Abstract: Retinopathy of prematurity is a devastating vascular disease of premature infants. A number of studies indicate that retinal function is affected in this disease. Using the rat model of oxygen-induced retinopathy, it is possible to explore more fully the complex relationship between neuronal, glial and vascular pathology in this condition. This review examines the structural and functional changes that occur in the rat retina following oxygen-induced retinopathy. We highlight that vascular pathology in rats is characterized by aberrant growth of blood vessels into the vitreous at the expense of blood vessel growth into the body of the retina. Moreover, amino acid neurochemistry, a tool for examining neuronal changes in a spatially complete manner reveals widespread changes in amacrine and bipolar cells. In addition, neurochemical anomalies within inner retinal neurons are highly correlated with the absence of retinal vessels. The key cell types that link blood flow with neuronal function are macroglia. Macroglia cells, which in the retina include astrocytes and Müller cells, are affected by oxygen-induced retinopathy. Astrocyte loss occurs in the peripheral retina, while Müller cells show signs of reactive gliosis that is highly localized to regions that are devoid of intraretinal blood vessels. Finally, we propose that treatments, such as blockade of the renin-angiotensin system, that not only targets pathological angiogenesis, but that also promotes re-vascularization of the retina are likely to prove important in the treatment of those with retinopathy of prematurity.
Publisher: Public Library of Science (PLoS)
Date: 27-05-2014
Publisher: Springer Science and Business Media LLC
Date: 24-04-2017
Publisher: Informa UK Limited
Date: 11-2002
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 05-2015
Abstract: To induce chronic intraocular pressure (IOP) elevation in rat eyes by circumlimbal suture. Anesthetized (isoflurane) Long-Evans rats underwent unilateral circumlimbal suture implantation while the fellow eyes served as untreated controls (n = 15). A sham group (n = 8) received the same procedure except that the suture was loosely tied. Intraocular pressure, electroretinography (ERG), and optical coherence tomography (OCT) were monitored for 15 weeks, after which retinal histology and immunofluorescence staining for glial fibrillary acidic protein (GFAP) and ionized calcium binding adapter molecule-1 (Iba-1) were undertaken. Both IOP and ERG remained unaltered in the sham and all control eyes over 15 weeks. In the ocular hypertensive eye, IOP spiked from 17 ± 1 to 58 ± 3 mm Hg immediately after suture application, recovering to 32 ± 2 mm Hg by 24 hours, and remained elevated by 7 to 10 mm Hg above baseline for 15 weeks. At week 2, there was a small reduction of ERG components involving the photoreceptor a-wave, bipolar cell b-wave, and ganglion cell-mediated scotopic threshold response (pSTR). The reduction in a- and b-wave remained stable, while the pSTR became more affected from week 8 onward (P < 0.05). By week 12, there was progressive retinal nerve fiber layer (RNFL) thinning. At week 15, GFAP expression was upregulated in inner retina and on Müller cells. The ganglion cell dysfunction was associated with RNFL thinning and cell loss in the ganglion cell layer. Circumlimbal suture provides a simple and cost-effective way to induce mild chronic ocular hypertension in rat eyes. This model produces preferential ganglion cell dysfunction and RNFL reduction.
Publisher: Elsevier BV
Date: 06-2009
DOI: 10.1016/J.NEUROSCIENCE.2009.02.084
Abstract: The bio-active peptide, angiotensin II (Ang II), has been suggested to exert a neuromodulatory effect on inner retinal neurons. In this study, we examined the distribution of angiotensin receptors (ATRs) in the developing and mature rat retina and optic nerve using immunofluorescence immunocytochemistry. Double-labeling experiments were performed with established markers to identify different retinal cell populations. In adult retinae, ATRs were observed on neurons involved in "ON" pathways of neurotransmission. Angiotensin II type 1 receptors (AT(1)Rs) were expressed by a sub-population of "ON" cone bipolar cells that also labeled for G alpha(0) and islet-1. Extra-neuronal expression of AT(1)Rs was evident on retinal astrocytes, Müller cells and blood vessels. Immunoreactivity for the angiotensin II type 2 receptor (AT(2)R) was observed on conventional and displaced GABAergic amacrine cells. Co-localization studies showed that AT(2)R-expressing amacrine cells constituted at least two separate sub-populations. Cell counts revealed that all wide-field amacrine cells expressing protein kinase C-alpha were also AT(2)R-positive a further subset of amacrine cells expressing AT(2)Rs and stratifying in sublamina "b" of the inner plexiform layer (IPL) was identified. Developmental expression of AT(1)Rs was dynamic, involving multiple inner neuronal classes. At postnatal day 8 (P8), AT(1)R immunoreactivity was observed on putative ganglion cells. The characteristic bipolar cell labeling observed in adults was not evident until P13. In contrast, AT(2)Rs were detected as early as P2 and localized specifically to amacrine cells from this age onward. These data provide further evidence for the potential role of angiotensin II in the modulation of retinal neurons and glia. The differential pattern of expression of these receptors across these cell types is similar to that observed in the brain and suggests that a similar functional role for Ang II may also exist within the retina.
Publisher: Wiley
Date: 20-12-2015
DOI: 10.1111/OPO.12174
Abstract: To assess ocular blood flow responses to acute IOP stress following 4 weeks of chronic IOP elevation in streptozotocin (STZ)-induced diabetic and control rats. We hypothesise that chronic IOP elevation for 4 weeks will further impair blood flow regulation in STZ-induced diabetic rats eyes. Two weeks following citrate buffer or STZ-injections chronic IOP elevation was induced in Long Evans rats via fortnightly intracameral injections of microspheres (15 μm) suspended in 5% polyethylene glycol. IOP was monitored daily. Electroretinography (ERG, -6.79-2.07 log cd s m(-2) ) was undertaken at Week 4 to compare photoreceptor (RmPIII ), ON-bipolar cell (Vmax ) and ganglion cell dominant ERG [scotopic threshold response (STR)] components. 4 weeks post-chronic IOP induction, ocular blood flow (laser Doppler flowmetry) was measured in response to acute IOP challenge (10-100 mmHg, in 5 mmHg steps, each 3 min). Four weeks of chronic IOP (mean ± S.E.M., citrate: 24.0 ± 0.3 to 30.7 ± 1.3 and STZ-diabetes: 24.2 ± 0.2 to 31.1 ± 1.2 mmHg) was associated with reduced photoreceptor litude in both groups (-25.3 ± 2.2% and -17.2 ± 3.0%, respectively). STZ-diabetic eyes showed reduced photoreceptor sensitivity (citrate: 0.5 ± 1.8%, STZ-diabetic: -8.1 ± 2.4%). Paradoxically ON-bipolar cell sensitivity was increased, particularly in citrate control eyes (citrate: 166.8 ± 25.9%, STZ-diabetic: 64.8 ± 18.7%). The ganglion cell dominant STR was not significantly reduced in STZ-diabetic rats. Using acute IOP elevation to probe autoregulation, we show that STZ-diabetes impaired autoregulation compared with citrate control animals. The combination of STZ-diabetes and chronic IOP elevation further impaired autoregulation. STZ-diabetes and chronic IOP elevation appear to be additive risk factors for impairment of ocular blood flow autoregulation.
Publisher: Informa UK Limited
Date: 02-05-2020
Publisher: Springer Science and Business Media LLC
Date: 24-11-2013
DOI: 10.1007/S00417-012-2212-4
Abstract: We consider whether pre-existing streptozotocin induced hyperglycemia in rats affects the ability of the eye to cope with a single episode of acute intraocular pressure (IOP) elevation. Electroretinogram (ERG) responses were measured (-6.08 to 1.92 log cd.s.m(-2)) in anaesthetized (60:5 mg/kg ketamine:xylazine) dark-adapted (>12 h) adult Sprague-Dawley rats 1 week after a single acute IOP elevation to 70 mmHg for 60 min. This was undertaken in rats treated 11 weeks earlier with streptozotocin (STZ, n = 12, 50 mg/kg at 6 weeks of age) or citrate buffer (n = 12). ERG responses were analyzed to derive an index of photoreceptor (a-wave), ON-bipolar (b-wave), amacrine (oscillatory potentials) and inner retinal (positive scotopic threshold response, pSTR) function. One week following acute IOP elevation there was a significant reduction of the ganglion cell pSTR (-35 ± 11 %, P = 0.0161) in STZ-injected animals. In contrast the pSTR in citrate-injected animals was not significant changed (+16 ± 14 %). The negative component of the STR was unaffected by IOP elevation in either citrate or STZ-treated groups. Photoreceptoral (a-wave, citrate-control +4 ± 3 %, STZ +4 ± 5 %) and ON-bipolar cell (b-wave, control +4 ± 3 %, STZ +4 ± 5 %) mediated responses were not significantly affected by IOP elevation in either citrate- or STZ-injected rats. Finally, oscillatory potentials (citrate-control +8 ± 23 %, STZ +1 ± 17 %) were not reduced 1 week after IOP challenge. The ganglion cell dominated pSTR was reduced following a single episode of IOP elevation in STZ diabetic, but not control rats. These data indicate that hyperglycemia renders the inner retina more susceptible to IOP elevation.
Publisher: Elsevier BV
Date: 2008
DOI: 10.1016/J.PRETEYERES.2007.09.003
Abstract: The flash electroretinogram (ERG) represents a serial ensemble of neural responses that can be used to objectively evaluate retinal function on a layer-by-layer basis. In this review, the seminal concepts of Granit are developed within the modern context to demonstrate how the ERG waveform can be decomposed to isolate the activity of in idual neural populations and their circuitry. The contribution of rods and cones to the ERG waveform can be precisely defined with simple methods that yield the veridical cone response, which allows identification of rod-isolated components. This knowledge will afford an enhanced capacity to understand retinal development and ageing as well as to interpret the effects of insult, genetic manipulation and disease processes on photoreceptor and neuron-specific components. This review integrates conclusions drawn from a large body of past work and presents new data that enables the provision of detailed methodology for ERG assessment in rodents. Emphasis is placed on protocols that allow efficient acquisition of useful information for the major ERG components with minimal complexity. In particular, specific guidelines for the isolation of rod and cone contributions from the full-field ERG in rodents are provided. This is complemented with detailed and novel methodology for determining parameters that describe in idual neuronal generators of rod and cone responses. The effect of stimulus energy on the kinetics of ERG response recovery and photopigment bleaching and regeneration are also discussed. The guidelines presented here are applicable to a wide range of investigations of retinal disease in rodent models.
Publisher: Informa UK Limited
Date: 11-1980
Publisher: Wiley
Date: 06-2000
DOI: 10.1046/J.1442-9071.2000.00301.X
Abstract: This study considered whether the dynamics of flicker adaptation can be explained in terms of probability summation over time between independent ON- and OFF-processors. Foveal thresholds were measured for flickering probes, and for static ON- and OFF-probes that have durations consistent with the flicker duty cycle. Thresholds were obtained using a probe-flash stimulus onset asynchrony paradigm. The outcome of the experiment suggests that flicker thresholds are lower than the component ON- and OFF-thresholds, and that the flicker response can be predicted by assuming probability summation between the ON- and OFF-mechanisms.
Publisher: Springer Science and Business Media LLC
Date: 05-04-2011
DOI: 10.1007/S10633-011-9269-Y
Abstract: The electroretinogram is a widely used objective measure of visual function. The best characterised feature of the full-field dark-adapted flash ERG, is the earliest corneal negativity, the a-wave, which primarily reflects photoreceptoral responses. However, recent studies in humans and primates show that there are post-receptoral contributions to the a-wave. It is not clear if such contributions exist in the rat a-wave. We consider this issue in the rat a-wave, using intravitreal application of pharmacological agents that isolate post-receptoral ON-pathways and OFF-pathways. In anaesthetised adult long Evans rats, we show that the ON-pathway (2-amino-4-phosphonobutyric acid, APB sensitive) makes negligible contribution to the a-wave. In contrast, CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) or PDA (cis-piperidine-2,3-dicarboxylic acid) sensitive mechanisms modify the a-wave in two ways. First, for bright luminous energies, OFF-pathway inhibition (CNQX or PDA) results in a 22% reduction to the early phase of the leading edge of the a-wave up to 14 ms. Second, OFF-pathway inhibition removed a corneal negativity that resides between the a-wave trough and the b-wave onset.
Publisher: MyJove Corporation
Date: 29-06-2016
DOI: 10.3791/54160
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 07-2008
DOI: 10.1167/IOVS.07-1628
Abstract: To characterize the effect of repeated brief intraocular pressure (IOP) elevations and the effect of IOP fluctuation on retinal function. The effects of one, two, and four episodes (70 mm Hg, 15 minutes) are compared by defining the time course of functional recovery after insults. The effect of IOP variation is considered by comparing a constant with a varying insult, keeping a common IOP-time integral (one 60-minute vs. two 30-minute vs. four 15-minute insults 70 mm Hg). IOP elevation is induced by anterior chamber cannulation in anesthetized, dark-adapted rats (n = 5-7 per group). Electroretinograms are recorded every 6 minutes throughout each event. Recovery time course is modeled using a logistic function, and time for 50% recovery is compared by nonparametric bootstrap. Electroretinographic recovery becomes progressively slower with more IOP episodes for bipolar cell and ganglion cell response (P 0.05). With regard to IOP variation, bipolar cell recovery after four 15-minute insults is faster than it is after two 30-minute insults (P < 0.05), which is faster than after one 60-minute insult (P < 0.05). Ganglion cell recovery after varying (four 15-minute and two 30-minute) insults is faster than after a constant (one 60-minute) insult (P < 0.05). This improved recovery with varying IOP challenge is greater for bipolar cell than for ganglion cell responses (P < 0.05). Repeated IOP insults lead to cumulative dysfunction in the inner retina. For the conditions used in this study, IOP variation per se is not detrimental but appears to be beneficial.
Publisher: Wiley
Date: 24-10-2017
DOI: 10.1111/OPO.12331
Abstract: This pilot study considered whether intraocular pressure ( IOP ) lowering could reverse ganglion cell dysfunction in a rat model of chronic ocular hypertension. A circumlimbal suture was applied in one eye to induce ocular hypertension ( n = 7) in Long‐Evans rats. The contralateral eye served as an untreated control. After 8 weeks of IOP elevation the suture was removed to lower IOP for the remaining 7 weeks. Electroretinogram ( ERG ) and optical coherence tomography ( OCT ) were measured at baseline, 2, 4, 8, 12 and 15 weeks. Retinae were collected for histology at week 15. In sutured eyes, IOP was elevated by 7–11 mmHg above control eyes (12 ± 0.2 mmHg [standard error of the mean]). Eight weeks of chronic IOP elevation resulted in a reduction of the ganglion cell mediated positive Scotopic Threshold Response ( pSTR , −25 ± 7% of baseline), as well as smaller photoreceptor (−7 ± 4%) and bipolar cell mediated responses (−6 ± 5%). After suture removal, IOP recovered to normal. By 15 weeks the a ‐wave (0 ± 6%), b ‐wave (−2 ± 6%) and pSTR had recovered back to baseline (from −25 ± 7% to −4 ± 6%). The retinal nerve fiber layer was thinned by −9 ± 3% at week 8 and showed no further decline at week 15 (−10 ± 2%). Cell numbers in the ganglion cell layer were similar between suture removal and control eyes at week 15 (3543 ± 478 vs 4057 ± 476 cells mm −2 ). The circumlimbal suture model might be a useful platform to study the reversibility of neuronal dysfunction from chronic IOP challenge.
Publisher: Wiley
Date: 23-09-2009
DOI: 10.1111/J.1471-4159.2009.06354.X
Abstract: Glutamate is a major neurotransmitter in the CNS but is also a key metabolite intimately coupled to amino acid production/degradation. We consider the effect of inhibition of two key glutamate metabolic enzymes: glutamine synthetase (GS) and aspartate aminotransferase on retinal function assessed using the electroretinogram to consider photoreceptoral (a-wave) and post-receptoral (b-wave) litudes. Quantitative immunocytochemistry was used to assess amino acid levels within photoreceptors, ganglion and Müller cells secondary to GS inhibition. Intravitreal injections of methionine sulfoximine reduced GS immunoreactivity in the rat retina. Additionally, glutamate and its precursor aspartate was reduced in photoreceptors and ganglion cells, but elevated in Müller cells. This reduction in neuronal glutamate was consistent with a deficit in neurotransmission (-75% b-wave reduction). Exogenous glutamine supply completely restored the b-wave, whereas other amino acid substrates (lactate, pyruvate, alpha-ketoglutarate, and succinate) only partially restored the b-wave (16-20%). Inhibition of the aminotranferases using aminooxyacetic acid had no effect on retinal function. However, aminooxyacetic acid application after methionine sulfoximine further reduced the b-wave (from -75% to -92%). The above data suggest that de novo glutamate synthesis involving aspartate aminotransferase can partially sustain neurotransmission when glutamate recycling is impaired. We also show that altered glutamate homeostasis results in a greater change in amino acid distribution in ganglion cells compared with photoreceptors.
Publisher: Elsevier BV
Date: 2005
DOI: 10.1016/J.JNEUMETH.2004.05.005
Abstract: We demonstrate that cathode-ray-tube (CRT) monitors commonly used as stimulus generators in visual neuroscience produce signal artefacts. This arises from two factors, one being the finite time needed for the raster scan of the CRT to cross the receptive field being stimulated, and the other being the restraint imposed by the impulse response of the phosphor itself. Together these factors result in smearing or blurring that manifests as high frequency noise, distorting the desired signal applied by the investigator. Our analysis identifies those conditions that promote these artefacts and we describe methods for their minimisation. We suggest that a monitor frame rate >/=100 Hz provides a reasonable trade-off between refresh and the generators of high frequency noise.
Publisher: Frontiers Media SA
Date: 10-02-2017
Publisher: Elsevier BV
Date: 05-1995
DOI: 10.1016/0042-6989(94)00226-C
Abstract: The aim of this study was to determine the minimum daily period of exposure to normal visual stimulation required to prevent occlusion induced myopia in chicks. Chicks were treated with monocular translucent occlusion in a 12 hr light/12 hr dark cycle. Occluders were removed for 0 (constant occlusion), 15, 20, 30, 40, 60, 75, 90, 120, 150, 240 or 720 (no occlusion) minutes each day for either 2 or 3 weeks. Fellow eyes and the eyes of normal chicks (bilaterally unoccluded) were used as controls. Occlusion-induced myopia and axial elongation were found to decrease significantly (P < 0.01) with increasing daily exposure to normal visual stimulation. Application of a time series equation to the data estimates that 30 and 130 min of normal visual exposure per day reduces myopia by 50 and 95% respectively. This study demonstrated that the regulation of ocular growth is affected strongly by short periods of normal visual stimulation in the presence of long periods of abnormal stimulation.
Publisher: Springer Science and Business Media LLC
Date: 12-10-2005
DOI: 10.1007/S00417-005-0121-5
Abstract: We develop the logic for a stimulus that can evaluate cone-dependent spatial summation and detail the modelling and interpretation of thresholds obtained with this stimulus. Fifteen observers participated, including two young normals tested extensively in control experiments, and a clinical trial based on four observers with age-related macular degeneration (AMD), four age-similar controls and five young observers. Monocular spatial summation functions were measured with contrast-modulated Gabor targets that approximated the optimal visual contrast detector. Thresholds were returned from a yes/no adaptive psychophysical algorithm. By fine titration along the size domain it was demonstrated that the spatial summation of normal observers can be adequately described by a two-component model. A reduced set of variables are proposed for clinical applications and the model was applied to data derived using these variables in persons with AMD and age-similar controls. We do not find a significant age-related loss of contrast sensitivity in our normal group. On the other hand, persons with early AMD exhibited a 0.41 log unit loss of sensitivity (P=0.04) from age-similar controls, without any change in their maximum summation area (A(max)). The nature of the spatial summation is consistent with the interpretation that early AMD produces a decrease in cone input to post-receptoral mechanisms in the absence of neural remodelling.
Publisher: Wiley
Date: 07-04-2011
DOI: 10.1111/J.1474-9726.2011.00690.X
Abstract: Mouse models that accumulate high levels of mitochondrial DNA (mtDNA) mutations owing to impairments in mitochondrial polymerase γ (PolG) proofreading function have been shown to develop phenotypes consistent with accelerated aging. As increase in mtDNA mutations and aging are risk factors for neurodegenerative diseases, we sought to determine whether increase in mtDNA mutations renders neurons more vulnerable to injury. We therefore examined the in vivo functional activity of retinal neurons and their ability to cope with stress in transgenic mice harboring a neural-targeted mutant PolG gene with an impaired proofreading capability (Kasahara, et al. (2006) Mol Psychiatry11(6):577-93, 523). We confirmed that the retina of these transgenic mice have increased mtDNA deletions and point mutations and decreased expression of mitochondrial oxidative phosphorylation enzymes. Associated with these changes, the PolG transgenic mice demonstrated accelerated age-related loss in retinal function as measured by dark-adapted electroretinogram, particularly in the inner and middle retina. Furthermore, the retinal ganglion cell-dominant inner retinal function in PolG transgenic mice showed greater vulnerability to injury induced by raised intraocular pressure, an insult known to produce mechanical, metabolic, and oxidative stress in the retina. These findings indicate that an accumulation of mtDNA mutations is associated with impairment in neural function and reduced capacity of neurons to resist external stress in vivo, suggesting a potential mechanism whereby aging central nervous system can become more vulnerable to neurodegeneration.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 27-03-2013
Abstract: To consider the hypothesis that streptozotocin (STZ)-induced hyperglycemia renders rat retinal function and ocular blood flow more susceptible to acute IOP challenge. Retinal function (electroretinogram [ERG]) was measured during acute IOP challenge (10100 mm Hg, increments of 5 mm Hg, 3 minutes per step, vitreal cannulation) in adult Long-Evans rats (6 weeks old citrate: n = 6, STZ: n = 10) 4 weeks after citrate buffer or STZ (65 mg/kg, blood glucose >15 mM) injection. At each IOP, dim and bright flash (-4.56, -1.72 log cd x s x m(-2)) ERG responses were recorded to measure inner retinal and ON-bipolar cell function, respectively. Ocular blood flow (laser Doppler flowmetry citrate: n = 6, STZ: n = 10) was also measured during acute IOP challenge. Retinas were isolated for quantitative PCR analysis of nitric oxide synthase mRNA expression (endothelial, eNos inducible, iNos neuronal, nNos). STZ-induced diabetes increased the susceptibility of inner retinal (IOP at 50% response, 60.1, CI: 57.0-62.0 mm Hg versus citrate: 67.5, CI: 62.1-72.4 mm Hg) and ON-bipolar cell function (STZ: 60.3, CI: 58.0-62.8 mm Hg versus citrate: 65.1, CI: 61.9-68.6 mm Hg) and ocular blood flow (43.9, CI: 40.8-46.8 versus citrate: 53.4, CI: 50.7-56.1 mm Hg) to IOP challenge. Citrate eyes showed elevated eNos mRNA (+49.7%) after IOP stress, an effect not found in STZ-diabetic eyes (-5.7%, P 0.05) following IOP elevation. STZ-induced diabetes increased functional susceptibility during acute IOP challenge. This functional vulnerability is associated with a reduced capacity for diabetic eyes to upregulate eNos expression and to autoregulate blood flow in response to stress.
Publisher: Public Library of Science (PLoS)
Date: 16-02-2012
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 08-2006
DOI: 10.1167/IOVS.05-1569
Abstract: The present study investigated retinal integrity in high myopia using spatial psychophysical tasks. Ten axial high myopes (-8.5 to -11.5 D) and 10 age-matched control subjects (+/-1.0 D) were recruited. All participants underwent clinical examination and ocular biometry and demonstrated no visible macular disease with visual acuities better than 6/12. Foveal summation thresholds were determined for white and S-cone-isolating spots of various diameters up to 5.4 degrees and spatial contrast sensitivity to luminance sine wave gratings (0.5-9.7 cyc/deg). Data were analyzed after correction for the magnification induced by eye size and correcting lens power. Spatial summation for both white and S-cone-isolating spots showed a generalized loss of sensitivity at all spot sizes in myopes relative to control subjects (P = 0.01). Critical areas at maximum summation were significantly larger in myopes, for S-cone isolating spots only, after image size correction (P = 0.048). Sensitivity at maximum summation correlated negatively with vitreous chamber depth for both targets (P = 0.005). Sensitivities for S-cone and luminance spots also correlated (P < 0.001), indicating widespread dysfunction. Myopes displayed contrast sensitivity losses at high spatial frequencies (P </= 0.006) with a normal peak contrast sensitivity. These data can be interpreted to indicate that highly myopic eyes have either (1) a reduction in the number of receptors and/or a reduction in their sensitivity or, (2) a reduction in the sensitivity of postreceptoral processes. The presence of normal contrast sensitivity at low spatial frequencies indicates dysfunction at a postreceptoral level in high myopes.
Publisher: Informa UK Limited
Date: 1990
Publisher: Institution of Engineering and Technology (IET)
Date: 2010
DOI: 10.1049/EL.2010.2242
Publisher: Wiley
Date: 07-2006
DOI: 10.1111/J.1460-9568.2006.04895.X
Abstract: Extracellular ATP mediates fast excitatory neurotransmission in many regions of the central nervous system through activation of P2X receptors. Although several P2X receptor subunits have been identified in the mammalian retina, little is known about the functional role of these receptors in retinal signalling. The purpose of the present study was to investigate whether purinergic P2X(7) receptors are involved in outer retinal processing by assessing receptor localization, degradation of extracellular ATP and the effect of functional activation of P2X(7) receptors on the electroretinogram (ERG). Using light and electron microscopy, we demonstrated that P2X(7) receptors are expressed postsynaptically on horizontal cell processes as well as presynaptically on photoreceptor synaptic terminals in both the rat and marmoset retina. Using an enzyme cytochemical method, we showed that ecto-ATPases are active in the outer plexiform layer of the rat retina, providing a mechanism by which purinergic synaptic transmission can be rapidly terminated. Finally, we evaluated the role of P2X(7) receptors in retinal function by assessing changes to the ERG response of rats after intravitreal delivery of the P2X(7) receptor agonist benzoyl benzoyl ATP (BzATP). Intravitreal injection of BzATP resulted in a sustained increase (up to 58%) in the litude of the photoreceptor-derived a-wave of the ERG. In contrast, BzATP caused a transient reduction in the rod- and cone-derived postreceptoral responses. These results provide three lines of evidence for the involvement of extracellular purines in outer retinal processing.
Publisher: Informa UK Limited
Date: 03-2011
DOI: 10.1111/J.1444-0938.2010.00564.X
Abstract: Although intraocular pressure (IOP) remains an important risk factor for glaucoma, it is clear that other factors can also influence disease development and progression. More recently, the role that blood pressure (BP) has in the genesis of glaucoma has attracted attention, as it represents a clinically modifiable risk factor and thus provides the potential for new treatment strategies beyond IOP reduction. The interplay between blood pressure and IOP determines the ocular perfusion pressure (OPP), which regulates blood flow to the optic nerve. If OPP is a more important determinant of ganglion cell injury than IOP, then hypotension should exacerbate the detrimental effects of IOP elevation, whereas hypertension should provide protection against IOP elevation. Epidemiological evidence provides some conflicting outcomes of the role of systemic hypertension in the development and progression of glaucoma. The most recent study showed that patients at both extremes of the blood pressure spectrum show an increased prevalence of glaucoma. Those with low blood pressure would have low OPP and thus reduced blood flow however, that people with hypertension also show increased risk is more difficult to reconcile. This finding may reflect an inherent blood flow dysregulation secondary to chronic hypertension that would render retinal blood flow less able to resist changes in ocular perfusion pressure. Here we review both clinical and experimental studies that have attempted to clarify the relationships among blood pressure, OPP and blood flow autoregulation in the pathogenesis of glaucoma.
Publisher: Informa UK Limited
Date: 05-1992
Publisher: Informa UK Limited
Date: 10-09-1999
Publisher: Informa UK Limited
Date: 16-08-2020
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 17-11-2011
DOI: 10.1167/IOVS.11-7602
Abstract: To investigate the effect of old age (3 vs. 18 months) on the retinal function of albino (Sprague-Dawley [SD]) and pigmented (Long-Evans [LE]) rats. Electroretinograms (ERG) were recorded in both albino (SD 3 months old n = 16, 18 months old n = 16) and pigmented (LE 3 months n = 16, 18 months n = 5) rats. Data are analyzed for photoreceptor, ON-bipolar, and retinal ganglion cell (RCG) litudes as well as photoreceptor and ON-bipolar cell sensitivities. In the pigmented strain, senescence results in decreased photoreceptor output, but ON-bipolar and retinal ganglion cell litudes were preserved, due to a relative increase in ON-bipolar cell sensitivity. In the albino rats, although ageing decreased both photoreceptor and ON-bipolar cell litudes, increased photoreceptor sensitivity produced a relative sparing of retinal ganglion cell litude. Both strains show evidence of retinal plasticity with senescence, albeit at different retinal levels. The exact mechanisms underlying sensitivity changes require further investigation. Nevertheless, given the findings of previous human studies, pigmented rats appear to be a more appropriate model for human ageing. Future work using animals to study the effect of ageing need careful consideration in strain selection.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 02-2004
DOI: 10.1167/IOVS.03-0695
Abstract: To test the proposal that inhibiting monocarboxylate transport in the rat retina results in altered retinal function measured using the electroretinogram (ERG) and to evaluate the efficacy of exogenous metabolic substrates to restore any functional deficit. Full-field white-flash ERGs were measured after monocarboxylate transport inhibition with intravitreal injection of alpha-cyano-4-hydroxycinnamic acid (4-CIN, 10 mM), and functional recovery was assessed after the introduction of various exogenous metabolic substrates (10 mM): lactate, pyruvate, alpha-ketoglutarate, alanine, succinate, and glutamine. The efficacy of glutamine as a metabolic substrate was also considered in the presence of phosphate-activated glutaminase inhibition (6-diazo-5-oxo-norleucin, 10 mM) or aminotransferase inhibition (aminooxyacetic acid, 10 mM). Pyruvate and alanine recovery was also assessed after aminooxyacetic acid application. 4-CIN application resulted in an increased phototransduction litude but a mild reduction of gain. A greater reduction of postreceptoral b-wave and oscillatory potential litudes (80%) was observed, along with delayed implicit times (35 ms). Partial recovery of b-wave litudes was achieved with exogenous lactate (24%), pyruvate (27%), alpha-ketoglutarate (27%), alanine (25%), and succinate (26%), whereas glutamine provided 62% recovery. However, none of the substrates improved phototransduction gain. Both 6-diazo-5-oxo-norleucin and aminooxyacetic acid completely suppressed the glutamine-induced b-wave recovery. Aminooxyacetic acid also abolished the b-wave recovery from 4-CIN afforded by pyruvate and alanine. The greater loss of the b-wave and oscillatory potentials may reflect preferential routing of amino acid carbon skeletons to oxidative metabolic pathways, which in turn reduces glutamate availability for neurotransmission between photoreceptors and ON-bipolar cells. The reduction in log S provides evidence that inhibition of monocarboxylate transport produced some metabolic dysfunction in the rat.
Publisher: Springer Science and Business Media LLC
Date: 03-2001
DOI: 10.1038/85354
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 2008
DOI: 10.1167/IOVS.06-1048
Abstract: A cathode-ray-tube (CRT) monitor-based technique was used to isolate clinically significant components of dark adaptation. The utility of the technique in identifying adaptation abnormalities in eyes with age-related maculopathy (ARM) is described. A CRT dark adaptometer was developed to assess cone and rod recovery after photopigment bleach. The following measures were obtained: cone recovery rate (R(c) in decades per minute) and absolute threshold (Tf(c) log candelas per square meter), rod recovery rate (R(r) decades per minute), and rod-cone transition (rod-cone break [RCB], in minutes). These components were isolated by appropriately selecting stimulus size, stimulus location, pigment bleach, and test duration and by coupling the CRT with judiciously selected neutral-density (ND) filters. The protocol was developed by using 5 young observers and was tested on 27 subjects with ARM in the study eye and 22 age-matched control subjects. The parameters necessary for effective isolation of cone and early phase rod dark adaptation were a 2.6 ND filter (for a standard CRT monitor, 0.08-80 cd . m(-2) luminance output) a 4 degrees foveated, 200-ms, achromatic spot approximately 30% pigment bleaching and a 30-minute test duration. These settings returned obvious rod and cone recovery curves in control and ARM eyes that were compatible with conventional test methods and identified 93% of participants with ARM as having delayed dynamics in at least one of the parameters. Cone recovery dynamics were significantly slower in the ARM group when compared with age-matched control subjects (R(c), 0.99 +/- 0.35 vs. 2.63 +/- 0.61 decades . min(-1), P < 0.0001). Three of the 27 eyes with ARM did not achieve RCB during the allowed duration (30 minutes). The remaining eyes with ARM (n = 24) exhibited a significant delay in rod recovery (R(r)(,) ARM, 0.16 +/- 0.03 vs. controls, 0.22 +/- 0.02 decades . min(-1), P < 0.0001) and the average time to RCB (+/-SD) in the ARM group was significantly longer than in the control subjects (19.12 +/- 5.17 minutes vs. 10.40 +/- 2.49 minutes, P < 0.0001). The CRT dark-adaptation technique described in this article is an effective test for identifying abnormalities in cone and rod recovery. Slowed cone and rod recovery and a delayed RCB were evident in the eyes with ARM. The test method is potentially useful for clinical intervention trials in which ARM progression is monitored.
Publisher: Elsevier BV
Date: 09-2000
DOI: 10.1016/S0042-6989(00)00121-8
Abstract: We investigated the interactions between flicker thresholds and luminance pedestals using threshold versus contrast (TvC) and method of constant stimuli paradigms. High litude luminance pedestals were found to elevate flicker thresholds, but low litude luminance pedestals were unable to reduce flicker thresholds. Luminance pedestals elevated flicker thresholds more at low temporal frequencies. A simple model based on local light adaptation was able to capture the general form of the TvC functions. Our results suggest that flicker thresholds derived in the presence of a luminance pedestal (luminance-pedestal flicker) may vary from those obtained by modulating about a mean luminance (mean-modulated flicker).
Publisher: Elsevier BV
Date: 04-1994
DOI: 10.1016/0042-6989(94)90039-6
Abstract: QUEST [Watson and Pelli, Perception and Psychophysics, 13, 113-120 (1983)] is an efficient method of measuring thresholds which is based on three steps: (1) Specification of prior knowledge and assumptions, including an initial probability density function (p.d.f.) of threshold (i.e. relative probability of different thresholds in the population). (2) A method for choosing the stimulus intensity of any trial. (3) A method for choosing the final threshold estimate. QUEST introduced a Bayesian framework for combining prior knowledge with the results of previous trials to calculate a current p.d.f. this is then used to implement Steps 2 and 3. While maintaining this Bayesian approach, this paper evaluates whether modifications of the QUEST method (particularly Step 2, but also Steps 1 and 3) can lead to greater precision and reduced bias. Four variations of the QUEST method (differing in Step 2) were evaluated by computer simulations. In addition to the standard method of setting the stimulus intensity to the mode of the current p.d.f. of threshold, the alternatives of using the mean and the median were evaluated. In the fourth variation--the Minimum Variance Method--the next stimulus intensity is chosen to minimize the expected variance at the end of the next trial. An exact enumeration technique with up to 20 trials was used for both yes-no and two-alternative forced-choice (2AFC) experiments. In all cases, using the mean (here called ZEST) provided better precision than using the median which in turn was better than using the mode. The Minimum Variance Method provided slightly better precision than ZEST. The usual threshold criterion--based on the "ideal sweat factor"--may not provide optimum precision efficiency can generally be improved by optimizing the threshold criterion. We therefore recommend either using ZEST with the optimum threshold criterion or the more complex Minimum Variance Method. A distinction is made between "measurement bias", which is derived from the mean of repeated threshold estimates for a single real threshold, and "interpretation bias", which is derived from the mean of real thresholds yielding a single threshold estimate. If their assumptions are correct, the current methods have no interpretation bias, but they do have measurement bias. Interpretation bias caused by errors in the assumptions used by ZEST is evaluated. The precisions and merits of yes-no and 2AFC techniques are compared.(ABSTRACT TRUNCATED AT 400 WORDS)
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 05-2003
DOI: 10.1167/IOVS.02-0769
Abstract: To evaluate cone visual function of subjects with age-related maculopathy (ARM). Cone thresholds in 16 patients with ARM and 14 age-matched control subjects were compared. All subjects had visual acuity of 6/12 or better in the studied eye. A range of contrast thresholds were measured to evaluate erse aspects of cone visual function under steady state conditions (spatiotemporal, color and luminance, and photopic sensitivity) or after bleaching (adaptation dynamics). ARM produced a diffuse loss across all cone steady state visual functions in 31% to 44% of subjects. The adaptation time constant of cone recovery was significantly prolonged in most (69%) ARM eyes. A cross-correlational analysis found adaptational kinetics to be independent of other steady state losses, with cone photopigment regeneration being the most affected visual function in ARM (chi(2) = 4.03, P < 0.05). The results show that cone-adaptational kinetics are affected in ARM more so than are steady state thresholds. Given that cone recovery is easy to examine in a clinical setting, this test may provide a useful index of photopic function in patients with ARM.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 20-02-2014
Abstract: The global or gross response index of visual performance measured from the eye does not necessarily translate to global responses measured from the brain. A better understanding of this relationship would facilitate the monitoring of disease models that affect the visual pathway. We consider whether rod- and cone-retino-cortical-pathways are equally affected by acute IOP elevation. Acute, stepwise IOP elevation (10, 30, 40, 50, 60, 70 mm Hg) was induced in anesthetized dark- (N = 8) and light-adapted pigmented rats (N = 6). Electroretinogram (ERG) and visual evoked potentials (VEP) were simultaneously measured after 10 minutes at each step. Relative litudes (treated/baseline, %) as a function of IOP level were described with a cumulative normal function. Our results showed decline in scotopic and photopic ERGs with IOP elevation. Photopic ERG responses were less sensitive to IOP challenge than scotopic ERG responses. Despite significant reductions of ganglion cell-mediated waveforms at 70 mm Hg, the VEP showed only subtle decreases in litude. Intraocular pressure elevation produced similar effects on rod- and cone-mediated VEP waveforms. We show that cone signals are less sensitive than rod ERGs to acute IOP challenge. Also, retinal signals are more sensitive than are cortical signals to IOP stress, suggesting that cortical processing may act to salvage reductions expected from attenuated retinal output.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 08-2008
DOI: 10.1167/IOVS.08-1735
Abstract: Diet-induced deficiencies in Omega-3 (omega-3) fatty acids are well known to alter photoreceptor function. In this study, the broader functional changes in a ersity of retinal neurons were considered. Sprague-Dawley dams were fed either omega-3-sufficient (omega-3(+), n = 21) or -deficient (omega-3(-), n = 19) diets 5 weeks before conception, with the pups continued on the mothers' diet. After 20 weeks of age, electroretinograms (ERGs) were recorded by using protocols that isolate separate cellular generators, including photoreceptors (PIII), ON-bipolar cells (PII), and ganglion/amacrine cells (STR). At the brightest energies, rod and cone responses were isolated with a paired-flash paradigm. Retinal tissue (omega-3(+), n = 5 omega-3(-), n = 5) was harvested at 23 weeks of age for fatty acid assays with thin layer and gas liquid chromatography. Omega-3 deficiency caused a 48.6% decrease in total retinal docosahexaenoic acid (DHA). This change induced significant litude decreases only in the rod PII (-8.2%) and positive (p)STR components (-27.4%), with widespread delays in all signals (PIII 5.7%, PII 13.6%, pSTR 7.6%, and negative [n]STR 8.3%). Omega-3 deficiency exerted its greatest effects on signals originating in the inner retina (pSTR). Increasing dietary omega-3 has beneficial effects across the retina, with the greatest improvement occurring in ganglion cell function.
Publisher: American Medical Association (AMA)
Date: 06-2012
DOI: 10.1001/ARCHOPHTHALMOL.2012.277
Abstract: To investigate the longitudinal changes in flicker perimetry in patients with age-related macular degeneration (AMD) as the condition progresses from early AMD to geographic atrophy (GA) or choroidal neovascularization (CNV). Patients with AMD and control subjects were recruited from a longitudinal study of retinal function in early AMD consisting of 187 participants. Only those who completed at least 4 consecutive, 6-monthly flicker perimetry tests were selected for this study. Study groups consisted of everyone who went on to develop GA (n = 16) or CNV (n = 5), controls (n = 24), and the high-risk, early- AMD participants whose eyes did not progress to GA or CNV (drusen >125 μm n = 18). The flicker sensitivity was determined, and its rate of change during the 18 months before the clinical detection of late AMD was calculated. Eyes that went on to develop GA or CNV had a significantly reduced mean (SD) flicker sensitivity in the months before clinical detection of GA (15.8 [5.6] dB) or CNV (19.1 [3.8] dB) compared with control eyes (22.9 [3.0] dB) (P < .001) and with eyes that did not progress to GA or CNV (21.4 [3.4] dB) (P < .001). The rate of change in flicker sensitivity was significantly increased in GA eyes (-0.07 dB/mo) (P < .001) but not in CNV eyes (0.006 dB/mo) (P = .56) compared with the control eyes (-0.003 dB/mo). Flicker sensitivity is reduced in eyes that go on to develop late AMD. The rate of change in flicker sensitivities over time was particularly useful in predicting eyes and areas within the eye that subsequently develop GA.
Publisher: Springer Science and Business Media LLC
Date: 06-1987
DOI: 10.1007/BF00140454
Abstract: Mucopolysaccharidosis VI (MPS VI) is an inherited lysosomal storage disease caused by a mutation of the gene for arylsulfatase B (ASB). Of the thirty-one patients registered in Germany, almost fifty percent have a Turkish migration background. MPS VI is treated by enzyme replacement therapy (ERT), which is time-consuming and expensive. This interdisciplinary study explored the illness perceptions and clinical treatment experiences among ten MPS VI patients with a Turkish migration background in two centers for metabolic diseases (Berlin and Mainz, Germany). The clinical treatment situation was observed and semi-structured interviews were conducted with patients and health care personnel, in addition to participatory observation in four patients' everyday environments in Berlin. The data from the interviews, patient records, and personal field notes were encoded, cross-related, and analyzed. Patients' acknowledgement of the disease and coping strategies are influenced predominantly by the perception of their in idual health status and the handling of the disease within their family. Patients' willingness to cooperate with treatment strategies is further modified by their knowledge of the disease and the relationships with their health care providers. In this analysis, cultural factors turned out to be marginally relevant. As with other chronic and debilitating diseases, effective treatment strategies have to reach beyond delivering medication. Health care providers need to strengthen the support for patients with a migration background. In this regard, they should respect the patients' cultural and social background and their personal perception of the disease and the therapy. Yet structural and social aspects (clinical setting, family and educational background) may be more crucial here than "cultural barriers."
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.JTOS.2018.10.004
Abstract: To investigate the ocular inflammatory response, using clinical and immunological techniques, in people experiencing contact lens (CL) discomfort. This study involved 38 adults who were full-time, silicone-hydrogel CL wearers. Participants were categorized into groups based upon a validated CL dry-eye questionnaire (CLDEQ-8) (n = 17 'asymptomatic', CLDEQ-8 score 0.05). The I-SOD was greater in symptomatic than asymptomatic CL wearers (23.1 ± 2.6 versus 11.3 ± 1.4 mOsmol/L, p = 0.001). People experiencing CL discomfort had higher tear IL-17A (122.6 ± 23.7 versus 44.0 ± 10.0 pg/mL, p = 0.02) and reduced tear stability (6.3 ± 1.1 versus 10.4 ± 1.6 s, p = 0.03) after several hours of CL wear. Tear IL-17A levels correlated with both the I-SOD (r = 0.43, p = 0.01) and CLDEQ-8 score (r = 0.40, p = 0.01). CL discomfort occurs in in iduals having no clinical dry eye signs, and is associated with higher tear levels of the pro-inflammatory cytokine IL-17A. These findings support an association between the discomfort response and low-grade, ocular surface inflammation.
Publisher: SAGE Publications
Date: 23-09-2020
Abstract: This article analyzes the impacts of the Australian Federal Government’s food labeling reforms on the formation of food practices and the market for local food products. It considers how the inclusion of product and ingredient origin information blurs the distinction between ‘domestic’ and ‘foreign’ food products, and foregrounds different ‘support local’ behaviors. Findings from the study highlight the influence of structural and cultural factors, complemented by the strategic use of media tools, in shaping how food labels function as mechanisms to mediate domestic and transnational food practices. Retail concentration, support for the ‘buy local’ discourse, and the mediating influence of supermarket food media are presented as key factors that underpin the diffusion of and the demand for branded products and local food products in Australia. The impacts of the food origin labeling regulations on Australia’s highly concentrated grocery retail sector and export markets for Australian food products are also discussed.
Publisher: Informa UK Limited
Date: 05-2000
DOI: 10.1111/J.1444-0938.2000.TB04909.X
Abstract: BACKGROUND: Glaucoma manifests mostly in the elderly, who frequently have otherocular changes that frustrate clear visualisation of the optic nerve head or nerve fibre layer. In the past, a large or asymmetric cup/disc ratio has been used to indicate the possibility of glaucoma. In this paper, I will argue that cup/disc ratios alone have poor sensitivity to glaucoma, and a more sophisticated approach is needed to make the earliest diagnosis. METHODS: This paper reviews the literature and describes the changes that occur at the optic nerve head and in the peripapillary region as a consequence of glaucomatous optic neuropathy (GON). RESULTS: The concept of 'risk factors' is developed to help screen for glaucoma. Glaucoma suspects require a full clinical investigation (visual field, IOP, assessment of anterior chamber, disc features and nerve fibres) and need to be monitored annually. For future reference, they should have their disc features recorded by instrumental methods or with photography at an early age. As no single sign provides the perfect diagnostic marker for the disease, clinicians need to examine for a group of signs before making the diagnosis. A clinical logic is developed in this paper to enhance the detection of glaucoma. CONCLUSION: Adoption of a protocol similar to that detailed in this paper will enhance the early and reliable detection of glaucoma.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 11-2006
DOI: 10.1167/IOVS.06-0590
Abstract: To evaluate the recovery of retinal function after acute IOP elevation. The electroretinogram (ERG) was measured before, during, and after IOP increased to 50 and 70 mm Hg at different durations in anesthetized, dark-adapted rats (n = 5-7). Signals were collected for dim and bright flashes (-4.95 and 1.0 log cd . s/m(2)) and analyzed in terms of the photoreceptoral (P3), postreceptoral (P2), and inner retinal (negative scotopic threshold response [nSTR]) responses. Parameters (treatment/baseline, %) were compared across time by using repeated-measures ANOVA and t-tests. The rate of recovery was quantified with a logistic function and compared by bootstrap. IOP spikes induce greater loss (P < 0.01) and slower recovery (P < 0.001) in the nSTR compared with the P2 and P3 responses. IOP spikes having common integral (pressure x duration, 2100 mm Hg x minutes) for insult gave significantly greater P2 and nSTR dysfunction at the higher pressure (70 vs. 50 mm Hg, nSTR reduced to -2.5% +/- 0.5% vs. 20.3% +/- 6.5%, P < 0.05). The higher pressure also produced significantly slower nSTR recovery (50% recovery time [t(0.5)] 70 vs. 50 mm Hg: 33.1 vs. 21.7 minutes P < 0.05). At a given IOP (70 mm Hg), t(0.5) showed a linear relationship with duration (15 vs. 30 vs. 60 minutes' exposure: t(0.5) 16.7 vs. 33.1 vs. 63.2 minutes P < 0.05) and integral. Ganglion cell function recovers slower than the outer retina after IOP insult, with peak IOP being the principle determinant of functional loss and recovery. For a fixed pressure, functional recovery is linearly related to exposure.
Publisher: Wiley
Date: 30-10-2010
DOI: 10.1002/CNE.22205
Abstract: Retinopathy of prematurity (ROP) is characterized by deficits in the scotopic pathway, although the cellular locus for these deficits is not clear. Here we examined neurochemical and cellular changes that develop during oxygen-induced retinopathy, a model of ROP. In addition, we examined whether treatment with the angiotensin II type-1 receptor inhibitor, valsartan, prevented these changes. Newborn Sprague-Dawley rats were exposed from postnatal day (P) 0 to 11 to 80%:20% O(2) (22:2 hr/day) and then room air until P18. Valsartan (40 mg/kg/day) was administered from P12-P18. Pattern recognition analysis of overlapping amino acid profiles was used to provide a statistically robust and spatially complete classification of neural elements for each experimental condition. Classification yielded 12 neuronal theme classes in controls and nine classes following ROP. ROP was associated with a reduction in the number of amacrine and bipolar cell theme classes. The reduction in theme classes was confirmed as true neuronal loss by quantifying anatomical changes and using an apoptotic marker. ROP was associated with shifts in amino acid levels across all neuronal populations except for horizontal cells. A reduction in the density of glycine-immunoreactive amacrine cells, and particularly parvalbumin-immunoreactive AII amacrine cells, was observed following ROP. Valsartan treatment during ROP prevented loss of theme classes and loss of AII amacrine cells. This study suggests that deficits in scotopic vision during ROP may be associated with loss of AII amacrine cells. In addition, this study highlights the potential of AT(1)R blockade in preventing neuronal anomalies in this condition.
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/262467
Abstract: Intraocular pressure (IOP) elevation is a key risk factor for glaucoma. Our understanding of the effect that IOP elevation has on the eye has been greatly enhanced by the application of the electroretinogram (ERG). In this paper, we describe how the ERG in the rodent eye is affected by changes in IOP magnitude, duration, and number of spikes. We consider how the variables of blood pressure and age can modify the effect of IOP elevation on the ERG. Finally, we contrast the effects that acute and chronic IOP elevation can have on the rodent ERG.
Publisher: Wiley
Date: 06-1999
DOI: 10.1046/J.1440-1606.1999.00193.X
Abstract: Purpose: Data is reported from an ongoing trial considering functional losses in patients with high‐risk drusen. We evaluate the temporal processing in 12 subjects: four patients with high‐risk drusen, four age‐matched controls and four young observers aged 22–30. Methods: Subjects were tested using frequency‐doubling technology, macula static and flicker fields on a Medmont perimeter and foveal temporal contrast sensitivity at 2, 5, 10 and 24 Hz. Results: Eyes with high‐risk drusen had good visual acuity (6/9.5 –2 or better). All control eyes had normal fields for static, flicker and frequency‐doubling perimetry. All high‐risk drusen eyes had normal static perimetry in the presence of abnormal flicker and frequency‐doubling perimetry. High‐risk drusen eyes showed a generalized loss of temporal sensitivity across all frequencies. Conclusions: We conclude that eyes with high‐risk drusen show losses to temporal stimuli in the presence of near‐normal acuity and static thresholds. We suggest that flickering stimuli might be useful for detecting and monitoring such patients.
Publisher: Wiley
Date: 29-08-2007
DOI: 10.1002/CNE.21478
Abstract: We established a metabolic and functional profile map of the normal rat retina, given the premise that: 1) amino acid neurochemistry reflects metabolic integrity and cellular identity, and 2) the permeation of a cation channel probe, agmatine (1-amino-4-guanidobutane, AGB), reflects cation channel functionality. The purpose was to provide a unique method of simultaneously assessing the metabolic and functional characteristics of the normal retina, upon which a comparison can be made to disease models. Quantitative pattern recognition analysis of overlapping amino acid and AGB expression profiles was used to provide a statistically robust classification of all neural elements according to their metabolic and functional characteristics. This classification was spatially complete and with single-cell resolution. The resulting classification demonstrated 28 statistically separable theme classes dominated by characteristic glutamate, GABA, glycine, and/or taurine profiles, with each of the neuronal theme classes containing further subtypes. The inclusion of a functional parameter (AGB mapping) in the classification process nearly doubled the number of neural elements that could be ascribed a neurochemical/cation profile, compared to when amino acid labeling was used alone. Strong endogenous glutamate gated AGB labeling was observed in horizontal cells, rod bipolar cells, cholinergic amacrine cells, and AII amacrine cells. The resulting amino acid and AGB profile matrix constitutes a nomogram for assessing cellular responses to experimental challenges in models of ocular disease.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 12-2005
DOI: 10.1167/IOVS.04-1009
Publisher: Elsevier BV
Date: 08-1997
DOI: 10.1016/S0042-6989(97)00033-3
Abstract: Achromatic losses in glaucoma would be expected to be greater than, or equal to, red-green chromatic losses if the following assumptions are made: (1) the function of the remaining axons is either unchanged or non-selectively reduced (2) red-green chromatic information is signaled by the midget ganglion cell system and (3) the function of the magnocellular system is reduced at least as much as that of the midget ganglion cells. This prediction was tested by measuring red-green (along with blue-yellow) mixture thresholds for 1 deg, 0.2 sec test spots presented on a color monitor on a white background of 50 cd/m2. Ellipses were fitted to plots of green contrast as a function of red contrast (or yellow as a function of blue), and major and minor axes of these ellipses were taken as measures of chromatic and achromatic thresholds, respectively. The study population consisted of 29 eyes in 29 patients with early glaucoma control data were derived from a data bank of 83 normal eyes. Red-green losses were significantly (P < 0.05) greater than achromatic losses in 6 out of the 11 eyes which showed significant losses of either chromatic or achromatic sensitivity (or both). It is concluded that, for these eyes, at least one of the above three assumptions is incorrect.
Publisher: Wiley
Date: 29-08-2007
DOI: 10.1002/CNE.21481
Abstract: We quantitatively tracked the recovery in amino acid labeling and cation channel functionality within distinct retinal elements for up to 2 weeks after an ischemic insult. Pattern recognition analysis of multiple amino acid and agmatine (a cation channel probe 1-amino-4-guanidobutane AGB) immunocytochemical patterns was used to classify all neural elements within the retina. This classification was spatially complete and with single-cell resolution. By 48 hours of reperfusion the amino acid labeling pattern of virtually all cell populations had returned to near preischemic levels, with the exception of glutamine and alanine levels, which remained significantly higher in many cell populations. Classification resulted in a total of 18 statistically separable theme classes (including neurons, glia, and extraretinal classes), a reduction of 10 theme classes from the normal retina (Sun et al. [ 2007a, b] J Comp Neurol, this issue). In addition to the known selective losses of amacrine cell types within the inner nuclear layer, we now demonstrate a selective loss of theme classes representing cone bipolar cells within the bipolar cell population. While there was a recovery in the amino acid labeling pattern, there were persistent cation channel gating anomalies (as reflected by AGB labeling) within several theme classes, including the theme class representing all the remaining rod bipolar cells, suggesting aberrant neuronal function secondary to metabolic insult.
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.OPHTHA.2017.06.028
Abstract: Recent developments in electronic technology are making it possible to home monitor the sensitivity of the central visual field using portable devices. We used simulations to investigate whether the higher test frequency afforded by home monitoring improves the early detection of rapid visual field loss in glaucoma and how any benefits might be affected by imperfect compliance or increased variability in the home-monitoring test. Computer simulation, with parameter selection confirmed with a cohort study. A total of 43 patients with treated glaucoma (both open-angle and closed-angle), ocular hypertension or glaucoma suspects (mean age, 71 years range, 37-89 years), were followed in the cohort study. We simulated series (n = 100 000) of visual fields for patients with stable glaucoma and patients with progressing glaucoma for 2 in-clinic (yearly and 6-monthly) and 3 home-monitoring (monthly, fortnightly, and weekly) schedules, each running over a 5-year period. Various percentages of home-monitored fields were omitted at random to simulate reduced compliance, and the variability of the home monitored fields also was manipulated. We used previously published variability characteristics for perimetry and confirmed their appropriateness for a home-monitoring device by measuring the device's retest variability at 2 months in a cohort of 43 patients. The criterion for flagging progression in our simulation was a significant slope of the ordinary least squares regression of a simulated patient's mean deviation (MD) data. The sensitivity for identifying rapid visual field loss (-2 decibels [dB]/year loss of MD). Although a sensitivity of 0.8 for rapid field loss was achieved after 2.5 years of 6-monthly testing in the clinic, weekly home monitoring achieved this by 0.9 years despite moderate test compliance of 63%. The improved performance of weekly home monitoring over 6-monthly clinical testing was retained even when home monitoring was assumed to produce more variable test results or be associated with low patient compliance. Detecting rapid visual field progression may be improved using a home-monitoring strategy, even when compliance is imperfect. The cost-benefit of such an approach is yet to be demonstrated, however.
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/352917
Abstract: The most dominant feature of the electroretinogram, the b-wave, is thought to reflect ON-bipolar cell responses. However, a number of studies suggest that the b-wave is made up of several components. We consider the composition of the rat b-wave by subtracting corneal negative components obtained using intravitreal application of pharmacological agents to remove postreceptoral responses. By analyzing the intensity-response characteristic of the PII across a range of fixed times during and after a light step, we find that the rat isolated PII has 2 components. The first has fast rise and decay characteristics with a low sensitivity to light. GABAc-mediated inhibitory pathways enhance this transient-ON component to manifest increased and deceased sensitivity to light at shorter ( ms) and longer times, respectively. The second component has slower temporal characteristics but is more sensitive to light. GABAc-mediated inhibition enhances this sustained-ON component but has little effect on its sensitivity to light. After stimulus offset, both transient and sustained components return to baseline, and a long latency sustained positive component becomes apparent. The light sensitivities of transient-ON and sustained-OFF components are consistent with activity arising from cone ON- and OFF-bipolar cells, whereas the sustained-ON component is likely to arise from rod bipolar cells.
Publisher: Springer Science and Business Media LLC
Date: 2002
Abstract: This paper considers the recommendation that Oscillatory Potentials (OP) be extracted by filtering in the frequency domain. This recommendation presumes that filtering isolates OPs from other ERG waveforms. However, we show that the leading edge of the a-wave has substantial frequency overlap with the OP spectrum at high intensities and that it contaminates these wavelets in the frequency domain. We propose a method of signal conditioning that removes a-waves prior to filtering. When this is done, the OPs show a bimodal distribution in the frequency domain that is well approximated by two Gaussians having means (+/-std. dev.) of 91.0 +/- 14.6 Hz and 153.1 +/- 17.1 Hz. This implies that two functions can be used to model the OPs in the time domain. However, we show that as most of the power of the Fourier spectrum (74%) is contained in a single Gaussian, a reasonable OP model can be derived by using a single function in the time domain. We test such a model on humans (n=5) and pigmented (n=14) and albino (n=14) guinea-pigs and show that it provides excellent fits to data across a range of flash exposures. Furthermore, changes in OP litude and timing between strains of guinea-pigs are easily detected with this model. We show that there is no statistical justification for making the model more complex by including multiple functions. Such paramatisation of the OP envelope provides a valuable and intuitive description of the OP waveforms in the time domain. The model provides an excellent description of OPs obtained with the current paradigm, however the single gaussian model may be deficient under stimulus conditions which produce highly asymmetric OP envelopes.
Publisher: Wiley
Date: 05-1999
DOI: 10.1007/S11745-999-0387-3
Abstract: The aim of this study was to compare two different strategies to elevate brain, retina, liver, and heart docosahexaenoic acid (DHA) levels in guinea pigs. First, we used an increasing dose of alpha-linolenic acid (ALA) relative to a constant linoleic acid (LA) intake, and second, we used two levels of dietary DHA provided in conjunction with dietary arachidonic acid (AA). The percentage DHA and AA of total phospholipids in retina, liver, and heart, and in the brain phosphatidylethanolamine and phosphatidylcholine was studied in female pigmented guinea pigs (3 wk old) fed one of five semisynthetic diets containing 10% (w/w) lipid for 12 wk. The LA content in the diets was constant (17% of total fatty acids), with the ALA content varying from 0.05% (diet SFO), to 1% (diet Mix), and to 7% (diet CNO). Two other diets (LCP1 and LCP3) had a constant LA/ALA ratio (17.5:1) but varied in the levels of dietary AA and DHA supplementation. Diet LCP1 was structured to closely replicate the principal long chain polyunsaturated fatty acids (PUFA) found in human breast milk and contained 0.9% AA and 0.6% DHA (% of total fatty acids) whereas diet LCP3 contained 2.7% AA and 1.8% DHA. At the end of the study, animals were sacrificed and tissues taken for fatty acid analyses. We found no significant effects of diets on the growth of guinea pigs. Diets containing ALA had profoundly different effects on tissue fatty acid compositions compared with diets which contained the long chain PUFA (DHA and AA). In the retina and brain phospholipids, high-ALA diets or dietary DHA supplementation produced moderate relative increases in DHA levels. There was no change in retinal or brain AA proportions following dietary AA supplementation, even at the highest level. This was in contrast to liver and heart where tissue DHA proportions were low and AA predominated. In these latter tissues, dietary ALA had little effect on tissue DHA proportions although the proportion of AA was slightly depressed at the highest dietary ALA intake, but dietary DHA and AA supplements led to large increases (up to 10-fold) in the proportions of these PUFA. Tissue uptake of dietary AA and DHA appeared maximal for the LCP1 diet (replicate of breast milk) in the heart. There were no significant changes in the plasma levels of 11-dehydrothromboxane B2 (a thromboxane A2 metabolite) for any diet. The data confirm that dietary ALA is less effective than dietary DHA supplementation (on a gram/gram basis) in increasing tissue DHA levels and that tissues vary greatly in their response to exogenous AA and DHA, with the levels of these long chain metabolites being most resistant to change in the retina and brain compared with liver and heart. Dietary DHA markedly increased tissue DHA proportions in both liver and heart, whereas the major effect of dietary AA was in the liver. Future studies of the effects of dietary DHA and AA supplementation should examine a variety of tissues rather than focusing only on neural tissue.
No related grants have been discovered for Algis Vingrys.