ORCID Profile
0000-0001-6496-3971
Current Organisation
Centre for Eye Research Australia
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Publisher: Springer Nature Singapore
Date: 2022
Publisher: Public Library of Science (PLoS)
Date: 03-11-2014
Publisher: Public Library of Science (PLoS)
Date: 16-02-2012
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: Public Library of Science (PLoS)
Date: 27-05-2014
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: 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: Public Library of Science (PLoS)
Date: 29-12-2014
Publisher: Public Library of Science (PLoS)
Date: 12-09-2013
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: 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: 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: 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: American Society for Clinical Investigation
Date: 13-07-2020
DOI: 10.1172/JCI127668
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: 08-2013
DOI: 10.1002/PHY2.55
No related grants have been discovered for Zheng He.