Image Defocus and Altered Retinal Gene Expression in Chick: Clues to the Pathogenesis of Ametropia

Stone, Richard A.; McGlinn, Alice M.; Baldwin, Donald; Tobias, John W.; Iuvone, P. Michael; Khurana, Tejvir S.

doi:10.1167/iovs.10-6727

Cited by 64 publications

(98 citation statements)

References 109 publications

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“…Visual form deprivation, which induces myopia, decreases retinal dopamine (Stone et al, 1989) and disrupts daily rhythms of eye growth (Weiss and Schaeffel, 1993). Expression profiling in chicken retina/RPE has also shown altered circadian clock gene and melatonin receptor expression in lens-induced myopia (Stone et al, 2011). Similar dopamine- and circadian clock-dependent eye growth regulatory mechanisms likely operate in the mammalian retina (Iuvove et al, 1989; Iuvone et al, 1991; Pardue et al, 2013; Stone et al 2013).…”

Section: The Retinal Clock’s Potential Role In Eye Diseasementioning

confidence: 99%

Circadian organization of the mammalian retina: From gene regulation to physiology and diseases

McMahon¹,

Iuvone²,

Tosini³

2014

Progress in Retinal and Eye Research

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149

181

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Section: The Retinal Clock’s Potential Role In Eye Diseasementioning

confidence: 99%

Circadian organization of the mammalian retina: From gene regulation to physiology and diseases

McMahon¹,

Iuvone²,

Tosini³

2014

Progress in Retinal and Eye Research

Self Cite

149

181

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“…Furthermore, form deprivation, which induces myopia, decreases retinal dopamine (Stone et al, 1989) and disrupts daily rhythms of eye growth (Weiss & Schaeffel, 1993). Gene expression profiling of chicken retina/RPE has also shown altered circadian clock gene and melatonin receptor expression in lens-induced myopia (Stone et al, 2011). …”

Section: Retinal Clock and Eye Diseasementioning

confidence: 99%

The Retina and Other Light-sensitive Ocular Clocks

Besharse

McMahon

2016

J Biol Rhythms

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Ocular clocks, first identified in the retina, are also found in the retinal pigment epithelium (RPE), cornea and ciliary body. The retina is a complex tissue of many cell types and considerable effort has gone into determining which cell types exhibit clock properties. Current data suggest that photoreceptors as well as inner retinal neurons exhibit clock properties with photoreceptors dominating in non-mammalian vertebrates and inner retinal neurons dominating in mice. However, these differences may in part reflect the choice of circadian output, and it is likely that clock properties are widely dispersed among many retinal cell types. The phase of the retinal clock can be set directly by light. In non-mammalian vertebrates direct light sensitivity is commonplace among body clocks, but in mice only the retina and cornea retain direct light-dependent phase regulation. This distinguishes the retina and possibly other ocular clocks from peripheral oscillators whose phase depends on the pace-making properties of the hypothalamic central brain clock, the suprachiasmatic nuclei (SCN). However, in mice retinal circadian oscillations dampen quickly in isolation due to weak coupling of its individual cell autonomous oscillators and there is no evidence that retinal clocks are directly controlled through input from other oscillators. Retinal circadian regulation in both mammals and non-mammalian vertebrates uses melatonin and dopamine as dark- and light-adaptive neuromodulators respectively, and light can regulate circadian phase indirectly through dopamine signaling. The melatonin/dopamine system appears to have evolved among non-mammalian vertebrates and retained with modification in mammals. Circadian clocks in the eye are critical for optimum visual function where they play a role fine tuning visual sensitivity, and their disruption can impact diseases such as glaucoma or retinal degeneration syndromes.

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“…Stone and colleagues (2011) used microchip technology to look at differential gene expression in chicken eyes wearing +15 D or −15 D lenses for hours or days. Few differentially expressed transcripts were found in eyes wearing positive lenses, but approximately 1500 transcripts were differentially expressed in eyes wearing negative lenses for 6 h. Not surprisingly, several of these were intrinsic clock genes, such as PER3 (Period homolog 3), and others related to rhythmic phenomena, such as melanopsin and a melatonin receptor.…”

Section: Expression Of Clock Genesmentioning

confidence: 99%

Ocular diurnal rhythms and eye growth regulation: Where we are 50 years after Lauber

Nickla¹

2013

Experimental Eye Research

107

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Many ocular processes show diurnal oscillations that optimize retinal function under the different conditions of ambient illumination encountered over the course of the 24 h light/dark cycle. Abolishing the diurnal cues by the use of constant darkness or constant light results in excessive ocular elongation, corneal flattening, and attendant refractive errors. A prevailing hypothesis is that the absence of the Zeitgeber of light and dark alters ocular circadian rhythms in some manner, and results in an inability of the eye to regulate its growth in order to achieve emmetropia, the matching of the front optics to eye length. Another visual manipulation that results in the eye growth system going into a “default” mode of excessive growth is form deprivation, in which a translucent diffuser deprives the eye of visual transients (spatial or temporal) while not significantly reducing light levels; these eyes rapidly elongate and become myopic. It has been hypothesized that form deprivation might constitute a type of “constant condition” whereby the absence of visual transients drives the eye into a similar default mode as that in response to constant light or dark. Interest in the potential influence of light cycles and ambient lighting in human myopia development has been spurred by a recent study showing a positive association between the amount of time that children spent outdoors and a reduced prevalence of myopia. The growing eyes of chickens and monkeys show a diurnal rhythm in axial length: Eyes elongate more during the day than during the night. There is also a rhythm in choroidal thickness that is in approximate anti-phase to the rhythm in eye length. The phases are altered in eyes growing too fast, in response to form deprivation or negative lenses, or too slowly, in response to myopic defocus, suggesting an influence of phase on the emmetropization system. Other potential rhythmic influences include dopamine and melatonin, which form a reciprocal feedback loop, and signal “day” and “night” respectively. Retinal dopamine is reduced during the day in form deprived myopic eyes, and dopamine D2 agonists inhibit ocular growth in animal models. Rhythms in intraocular pressure as well, may influence eye growth, perhaps as a mechanical stimulus triggering changes in scleral extracellular matrix synthesis. Finally, evidence shows varying influences of environmental lighting parameters on the emmetropization system, such as high intensity light being protective against myopia in chickens. This review will cover the evidence for the possible influence of these various factors on ocular growth. The recognition that ocular rhythms may play a role in emmetropization is a first step toward understanding how they may be manipulated in treatment therapies to prevent myopia in humans.

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Image Defocus and Altered Retinal Gene Expression in Chick: Clues to the Pathogenesis of Ametropia

Cited by 64 publications

References 109 publications

Circadian organization of the mammalian retina: From gene regulation to physiology and diseases

Circadian organization of the mammalian retina: From gene regulation to physiology and diseases

The Retina and Other Light-sensitive Ocular Clocks

Ocular diurnal rhythms and eye growth regulation: Where we are 50 years after Lauber

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