Gnaz couples the circadian and dopaminergic system to G protein-mediated signaling in mouse photoreceptors

Vancura, Patrick; Abdelhadi, Shaima; Csicsely, Erika; Baba, Kenkichi; Tosini, Gianluca; Iuvone, P. Michael; Spessert, Rainer

doi:10.1371/journal.pone.0187411

Cited by 14 publications

(18 citation statements)

References 64 publications

(78 reference statements)

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“…Clock genes are highly expressed in dopamine amacrine cells . Dopamine entrains circadian rhythms of gene expression in RPE, photoreceptors, and retinal ganglion cells, as well as the inner retinal rhythmic expression of the circadian reporter Per2 luciferase . Disruption of dopamine signaling disrupts circadian rhythms of cone ERG responses, contrast sensitivity, and protein phosphorylation in photoreceptor cells .…”

Section: Circadian Clocks and Melanopsinmentioning

confidence: 99%

Circadian rhythms, refractive development, and myopia

Chakraborty

Ostrin

Nickla

et al. 2018

Ophthalmic Physiologic Optic

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166

145

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Purpose Despite extensive research, mechanisms regulating postnatal eye growth and those responsible for ametropias are poorly understood. With the marked recent increases in myopia prevalence, robust and biologically-based clinical therapies to normalize refractive development in childhood are needed. Here, we review classic and contemporary literature about how circadian biology might provide clues to develop a framework to improve the understanding of myopia etiology, and possibly lead to rational approaches to ameliorate refractive errors developing in children. Recent findings Increasing evidence implicates diurnal and circadian rhythms in eye growth and refractive error development. In both humans and animals, ocular length and other anatomical and physiological features of the eye undergo diurnal oscillations. Systemically, such rhythms are primarily generated by the ‘master clock’ in the surpachiasmatic nucleus, which receives input from the intrinsically photosensitive retinal ganglion cells (ipRGCs) through the activation of the photopigment melanopsin. The retina also has an endogenous circadian clock. In laboratory animals developing experimental myopia, oscillations of ocular parameters are perturbed. Retinal signaling is now believed to influence refractive development; dopamine, an important neurotransmitter found in the retina, not only entrains intrinsic retinal rhythms to the light:dark cycle, but it also modulates refractive development. Circadian clocks comprise a transcription/translation feedback control mechanism utilizing so-called clock genes that have now been associated with experimental ametropias. Contemporary clinical research is also reviving ideas first proposed in the nineteenth century that light exposures might impact refraction in children. As a result, properties of ambient lighting are being investigated in refractive development. In other areas of medical science, circadian dysregulation is now thought to impact many non-ocular disorders, likely because the patterns of modern artificial lighting exert adverse physiological effects on circadian pacemakers. How, or if, such modern light exposures and circadian dysregulation contribute to refractive development is not known. Summary The premise of this review is that circadian biology could be a productive area worthy of increased investigation, which might lead to the improved understanding of refractive development and improved therapeutic interventions.

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Section: Circadian Clocks and Melanopsinmentioning

confidence: 99%

Circadian rhythms, refractive development, and myopia

Chakraborty

Ostrin

Nickla

et al. 2018

Ophthalmic Physiologic Optic

Self Cite

166

145

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“…Consistent with a significant role of clock-dependent gene regulation in retinal physiology, changes in transcript levels were seen to result in corresponding changes in protein amount. 55 , 61 , 62 , 64 …”

Section: Circadian Clocks In the Mammalian Retinamentioning

confidence: 99%

“… 15 Consistent with this concept, the clock-dependent release of dopamine from amacrine neurons 50 , 71 , 72 appears to contribute to rhythmicity of gene expression in photoreceptors. This follows from studies in melatonin-proficient mouse strains in which dopamine levels show a circadian rhythm 73 : in mice deficient for D 4 receptors, the periodicity of a subset of genes is attenuated in photoreceptors ( Acadm , Cpt-1α 62 ; Nr4a1 63 ; Gnaz 64 ).…”

Section: Circadian Clocks In the Mammalian Retinamentioning

confidence: 99%

Ocular Clocks: Adapting Mechanisms for Eye Functions and Health

Felder-Schmittbuhl

Buhr

Dkhissi-Benyahya

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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Vision is a highly rhythmic function adapted to the extensive changes in light intensity occurring over the 24-hour day. This adaptation relies on rhythms in cellular and molecular processes, which are orchestrated by a network of circadian clocks located within the retina and in the eye, synchronized to the day/night cycle and which, together, fine-tune detection and processing of light information over the 24-hour period and ensure retinal homeostasis. Systematic or high throughput studies revealed a series of genes rhythmically expressed in the retina, pointing at specific functions or pathways under circadian control. Conversely, knockout studies demonstrated that the circadian clock regulates retinal processing of light information. In addition, recent data revealed that it also plays a role in development as well as in aging of the retina. Regarding synchronization by the light/dark cycle, the retina displays the unique property of bringing together light sensitivity, clock machinery, and a wide range of rhythmic outputs. Melatonin and dopamine play a particular role in this system, being both outputs and inputs for clocks. The retinal cellular complexity suggests that mechanisms of regulation by light are diverse and intricate. In the context of the whole eye, the retina looks like a major determinant of phase resetting for other tissues such as the retinal pigmented epithelium or cornea. Understanding the pathways linking the cell-specific molecular machineries to their cognate outputs will be one of the major challenges for the future.

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“…In the inner retina, melatonin modulates dopamine release . Dopamine mediates light adaptation and circadian changes in visual sensitivity, and entrains circadian rhythms of gene expression in retinal pigment epithelium, photoreceptors, and retinal ganglion cells . Melatonin and dopamine are both under circadian control, and have antagonistic effects in the retina, with melatonin release in darkness, and dopamine release in response to light.…”

Section: Underlying Anatomy and Physiologymentioning

confidence: 99%

Ocular and systemic melatonin and the influence of light exposure

Ostrin

2019

Clinical and Experimental Optometry

111

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Melatonin is a neurohormone known to modulate a wide range of circadian functions, including sleep. The synthesis and release of melatonin from the pineal gland is heavily influenced by light stimulation of the retina, particularly through the intrinsically photosensitive retinal ganglion cells. Melatonin is also synthesised within the eye, although to a much lesser extent than in the pineal gland. Melatonin acts directly on ocular structures to mediate a variety of diurnal rhythms and physiological processes within the eye. The interactions between melatonin, the eye, and visual function have been the subject of a considerable body of recent research. This review is intended to provide a broad introduction for eye-care practitioners and researchers to the topic of melatonin and the eye. The first half of the review describes the anatomy and physiology of melatonin production: how visual inputs affect the pineal production of melatonin; how melatonin is involved in a variety of diurnal rhythms within the eye, including photoreceptor disc shedding, neuronal sensitivity, and intraocular pressure control; and melatonin production and physiological roles in retina, ciliary body, lens and cornea. The second half of the review describes clinical implications of light/melatonin interactions. These include light exposure and photoreceptor contributions in melatonin suppression, leading to consideration of how blue blockers, cataract, and light therapy might affect sleep and mood in patients. Additionally, the interactions between melatonin, sleep and refractive error development are discussed. A better understanding of environmental factors that affect melatonin and subsequent effects on physiological processes will allow clinicians to develop treatments and recommend modifiable behaviours to improve sleep, increase daytime alertness, and regulate ocular and systemic processes related to melatonin.

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Gnaz couples the circadian and dopaminergic system to G protein-mediated signaling in mouse photoreceptors

Cited by 14 publications

References 64 publications

Circadian rhythms, refractive development, and myopia

Circadian rhythms, refractive development, and myopia

Ocular Clocks: Adapting Mechanisms for Eye Functions and Health

Ocular and systemic melatonin and the influence of light exposure

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