Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Circadian and light-driven regulation of rod dark adaptation

ABSTRACT: The sensation of light is initiated in photoreceptor cells by the photoisomerization of a chromophore molecule from 11-cis to all-trans retinal. Continuous visual perception requires recycling of the spent chromophore back to the 11-cis form through the visual cycle, a series of reactions in the retinal pigmented epithelium (RPE). Light-driven chromophore consumption by photoreceptors is greater in daytime compared to night time, suggesting that correspondingly higher activity of the visual cycle may be required. On the other hand, as rod photoreceptors are saturated in bright light, the continuous turnover of their chromophore through the visual cycle during daytime would unnecessarily utilize precious energy and produce toxic byproducts. Here, we sought to determine whether the recycling of chromophore and the dark adaptation of rods is regulated by the circadian clock and light exposure. We demonstrate that in melatonin-proficient C3H/f+/+ mice, rod dark adaptation is slower during the day or after light exposure. This surprising daytime downregulation of the RPE visual cycle was further demonstrated by gene analysis, which revealed light-driven reduction in the expression of Rpe65, which encodes a key enzyme of the RPE visual cycle. In contrast, rods in melatonin-deficient strains (C57BL6/J and 129/Sv) were not affected by this daily visual cycle modulation. Our results demonstrate that the circadian clock and light exposure regulate the recycling of chromophore in the RPE visual cycle. This daily modulation of rod dark adaptation is mediated by melatonin and could potentially protect the retina from light-induced damage during the day. mRNA-seq of murine eyes (lens removed) in objective day (OD) vs. subjective day (SD) conditions (2 biological replicates per condition). Each biological replicate consisted of 4 eyes (from 1 female and 1 male).

ORGANISM(S): Mus musculus

SUBMITTER: Joseph Corbo

PROVIDER: E-GEOD-68470 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Tikidji-Hamburyan2018 - Rod phototransduction under strong illumination This model is described in the article: Rods progressively escape saturation to drive visual responses in daylight conditions. Tikidji-Hamburyan A, Reinhard K, Storchi R, Dietter J, Seitter H, Davis KE, Idrees S, Mutter M, Walmsley L, Bedford RA, Ueffing M, Ala-Laurila P, Brown TM, Lucas RJ, Münch TA. Nat Commun 2017 Nov; 8(1): 1813 Abstract: Rod and cone photoreceptors support vision across large light intensity ranges. Rods, active under dim illumination, are thought to saturate at higher (photopic) irradiances. The extent of rod saturation is not well defined; some studies report rod activity well into the photopic range. Using electrophysiological recordings from retina and dorsal lateral geniculate nucleus of cone-deficient and visually intact mice, we describe stimulus and physiological factors that influence photopic rod-driven responses. We find that rod contrast sensitivity is initially strongly reduced at high irradiances, but progressively recovers to allow responses to moderate contrast stimuli. Surprisingly, rods recover faster at higher light levels. A model of rod phototransduction suggests that phototransduction gain adjustments and bleaching adaptation underlie rod recovery. Consistently, exogenous chromophore reduces rod responses at bright background. Thus, bleaching adaptation renders mouse rods responsive to modest contrast at any irradiance. Paradoxically, raising irradiance across the photopic range increases the robustness of rod responses. This model is hosted on BioModels Database and identified by: MODEL1710030000. To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Circadian and light-driven regulation of rod dark adaptation

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