ORCID Profile
0000-0002-4516-1022
Current Organisation
James Cook University
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Publisher: Elsevier BV
Date: 02-2010
DOI: 10.1016/J.EXER.2009.10.011
Abstract: Changes in retinal crystallin gene expression have been implicated in the development of myopia in animal models. We therefore investigated the expression of alphaB-crystallin (cryab) in the chicken retina during periods of increased ocular growth induced by form-deprivation and negative lens-wear, and during periods of decreased ocular growth induced by diffuser removal from previously form-deprived eyes, and plus lens-wear. Cryab RNA transcript levels in the chicken retina were measured using semi-quantitative real-time RT-PCR, at times between 1 h and 10 days after the fitting of diffusers or negative lenses, and at times between 1 h and 3 days following the removal of diffusers from previously form-deprived eyes, or the addition of plus lenses. Changes in expression for each condition at each time-point are analysed relative to expression in retinas from age-matched untreated control birds. No change in relative expression of cryab RNA transcript was detected 1 h after fitting diffusers to induce form-deprivation myopia. A transient increase in cryab RNA transcript expression was detected around 1 day later (p = 0.02), but expression returned to control levels after three days. After 7 (p = 0.005) and 10 (p = 0.001) days, retinal cryab RNA transcript expression progressively increased relative to controls. After removal of the diffusers, to initiate recovery, cryab RNA transcript expression remained elevated, with only a slight return to control levels. During the development of lens-induced myopia, no changes in cryab RNA transcript expression relative to controls were seen on day 1, but increases were seen at 10 days (p = 0.004). No significant changes in retinal cryab RNA transcript expression were seen in response to plus lenses compared to either contralateral control values (MANOVA F = 0.60, p = 0.48) or age-matched untreated values (MANOVA F = 4.10, p = 0.08). Changes in retinal cryab RNA transcript expression were not systematically related to changes in the rate of eye growth. The role of the transient increase in cryab expression observed after 1 day of form-deprivation, which was not seen after fitting negative lenses, is unclear. The later increases in relative cryab expression seen during the development of form-deprivation and lens-induced myopia occur too late to have a major role in the differential regulation of eye growth between experimental and control eyes. Given that cryab is a member of the small heat shock protein family, the later increases may reflect the emergence of cell damage related to high myopic pathology in the experimentally enlarged eyes and retina.
Publisher: Wiley
Date: 15-03-2001
DOI: 10.1046/J.1471-4159.2001.00145.X
Abstract: Dopamine is generally accepted as a major neurotransmitter associated with light-adaptive processes in the retina. However, little is known about its precise release pattern in vivo, largely due to the lack of an unambiguous method for the determination of dopamine release. We have found that vitreal levels of dihydroxyphenylacetic acid (DOPAC) reflect the rate of dopamine release in chickens. Blocking re-uptake with nomifensine significantly lowered vitreal DOPAC and retinal dopamine, confirming the retinal origin and reliance of vitreal DOPAC on intact re-uptake mechanisms. Further, inhibition of monoamine oxidase with pargyline reduced vitreal as well as retinal DOPAC levels, confirming that the DOPAC detected is generated by monoamine oxidase. Finally, we found that DOPAC diffused freely into and out of isolated vitreous bodies and we found the vitreous to be metabolically inert with respect to DOPAC, supporting the idea that vitreal levels of DOPAC are consequential to the retinal metabolism of dopamine. Exposure to light, which is known to increase retinal dopamine release, readily increased vitreal DOPAC levels. The accumulation of DOPAC in the vitreous over 6 h light fitted a mathematical model of DOPAC accumulation based on zero-order influx (proportional to dopamine release rates) and diffusion driven, first-order efflux.
Publisher: Wiley
Date: 05-1996
Publisher: Elsevier BV
Date: 2006
DOI: 10.1016/J.NEUINT.2005.08.004
Abstract: The retinal dopaminergic system appears to play a major role in the regulation of global retinal processes related to light adaptation. Although most reports agree that dopamine release is stimulated by light, some retinal functions that are mediated by dopamine exhibit circadian patterns of activity, suggesting that dopamine release may be controlled by a circadian oscillator as well as by light. Using the accumulation of the dopamine metabolite dihydroxyphenylacetic acid (DOPAC) in the vitreous as a measure of dopamine release rates, we have investigated the balance between circadian- and light control over dopamine release. In chickens held under diurnal light:dark conditions, vitreal levels of DOPAC showed daily oscillations with the steady-state levels increasing nine-fold during the light phase. Kinetic analysis of this data indicates that apparent dopamine release rates increased almost four-fold at the onset of light and then remained continuously elevated throughout the 12h light phase. In constant darkness, vitreal levels of DOPAC displayed circadian oscillations, with an almost two-fold increase in dopamine release rates coinciding with subjective dawn/early morning. This circadian rise in vitreal DOPAC could be blocked by intravitreal administration of melatonin (10 nmol), as predicted by the model of the dark-light switch where a circadian fall in melatonin would relieve dopamine release of inhibition and thus be responsible for the slight circadian increase in dopamine release. The increase in vitreal DOPAC in response to light, however, was only partially suppressed by melatonin. The activity of the dopaminergic amacrine cell in the chicken retina thus appears to be dominated by light-activated input.
Publisher: Elsevier BV
Date: 07-2007
DOI: 10.1016/J.EXER.2007.02.019
Abstract: Increases in the expression of the immediate early gene ZENK in the retina, measured by changes in the levels of mRNA and protein immunoreactivity, are amongst the most rapid responses so far measured to conditions that decrease the rate of eye growth in chickens. Our aim was to determine whether atropine, a muscarinic cholinergic antagonist, and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide, a dopamine agonist, which are known to block excessive eye growth, produce similar changes in ZENK expression. Form-deprivation resulted in significant down-regulation of the expression of retinal ZENK mRNA within 1 h of fitting the diffusers, whereas removal of the diffusers from the eyes of chickens that had developed form-deprivation myopia resulted in significant up-regulation of retinal ZENK expression within 1 h. When atropine (10 microL of 25 mM solution) and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (10 microL of a 10 mM solution) were injected intravitreally, just prior to fitting the diffusers, the down-regulation of retinal ZENK mRNA caused by form-deprivation was reversed. This resulted in levels of ZENK mRNA higher than in control or contralateral control eyes. The doses were chosen because they are known to block the excessive axial elongation induced by form-deprivation, without affecting the growth of control eyes. Neither agent had any effect on retinal ZENK expression within this time period when injected into control eyes. These results suggest that both muscarinic acetylcholine antagonists and dopamine agonists act early in the signal cascade controlling eye growth, possibly within the retina itself.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2004
DOI: 10.1097/00006324-200402000-00013
Abstract: To use the technique of differential gene display to analyze changes in gene expression that occur during the development of and recovery from form-deprivation myopia. The differential display-reverse transcriptase-polymerase chain reaction technique was used to detect cDNAs that are differentially expressed after 24 h (including 12 h in the light) after fitting with a diffuser to induce form-deprivation myopia. Messenger RNA levels were determined by quantitative Northern blotting in retinas after 11 days of form deprivation or in retinas where the diffusers had been removed the previous day. Twenty-six differentially expressed genes were processed in our initial screen. Two of these, alphaB-crystallin and retinoic acid receptor-alpha, were studied further. Levels of alphaB-crystallin mRNA were increased on day 11 in retinas from form-deprived eyes relative to eyes of control chickens and were reduced to below those levels within 6 to 12 h after removal of the diffusers. Levels of retinoic acid receptor-alpha mRNA showed similar changes, except that after removal of the diffusers, the levels further increased. The technique of differential gene display can be used to detect changes in gene expression during the regulation of eye growth. The response of alphaB-crystallin is particularly interesting because expression increases when eye growth is high and decreases when eye growth slows.
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/J.EXER.2006.09.018
Abstract: Placing a translucent diffuser over the eye of a chick causes the eye to grow excessively, resulting in form-deprivation myopia. For chickens kept on a 12:12 h light/dark cycle, removing the diffuser for 3 h during the light period protects against the excessive growth, but if the bird is kept in the dark for this 3-h period, the protective effect is abolished. Injecting dopamine agonists into the eye during this 3-h dark period restores the protective effect, which can be blocked by dopamine antagonists injected just prior to diffuser removal in the light. These responses are mediated by D2 receptors, suggesting that the protective effect of normal vision against form-deprivation is mediated through the stimulation of dopamine release and activation of D2-dopamine receptors.
Publisher: Elsevier BV
Date: 09-2009
DOI: 10.1016/J.EXER.2009.04.003
Abstract: Genome-wide mapping studies have suggested a possible role for Pax6 in the development of myopia. We therefore investigated the expression of Pax6 RNA transcripts in the chicken retina during periods of increased ocular growth, induced by form-deprivation and negative lens-wear, and during periods of decreased ocular growth, induced by diffuser removal from previously form-deprived eyes, and plus lens-wear. Levels of Pax6 RNA transcripts in the chicken retina were measured using semi-quantitative real-time RT-PCR, at times between 1 h and 10 days after the fitting of diffusers or negative lenses, and at times between 1h and 3 days following the removal of diffusers from previously form-deprived eyes, or the addition of plus lenses. Pax6 expression was unaffected during the initial 3 days of the response to form-deprivation or negative lens-wear, when rapid rates of growth are well-established. Alterations in the expression of Pax6 RNA transcripts were only observed after 7-10 days of form-deprivation (7 days, -15.7 +/- 5.3% 10 days, -32.0 +/- 10.3%), with a similar response not seen during negative lens-wear, when eye growth also increases, suggesting that these alterations are specific to form-deprivation, rather to changes in the rate of eye growth. The late changes in Pax6 expression observed during form-deprivation were rapidly reversed after diffuser removal, with the levels of Pax6 RNA transcripts returning to those seen in control birds by 3 days (1 h, -27.8 +/- 4.7% 1 day, -16.9 +/- 4.8% 3 days + 1.0 +/- 8.6%). Analogous changes were not seen in response to positive lenses in which eye growth is also slowed. Overall, the findings of this study do not support a role for Pax6 in the modulation of ocular growth during visual manipulation.
No related grants have been discovered for Pamela Megaw.