Vitamin A cycle byproducts impede dark adaptation.
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ABSTRACT:
SUBMITTER: Zhang D
PROVIDER: S-EPMC8427233 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
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Project description:Purpose:Functional studies of rods in age-related macular degeneration using the Medmont Dark-Adapted Chromatic Perimeter (DACP) have demonstrated impairments in scotopic sensitivities and dark adaptation (DA). We investigated the intersession repeatability of scotopic sensitivity and DA parameters including the rod intercept time recorded from the Medmont DACP. Methods:Scotopic thresholds (14 test points) and DA using a 30% photobleach (eight test points) were measured on two separate days from participants 50 years of age or older with a range of age-related macular degeneration severity at loci superior and inferior to the fovea. Repeatability coefficients were calculated for prebleach scotopic sensitivity, and for DA parameters including rod intercept time. Results:Twelve participants (mean age, 79.7 ± 8.1 years) repeated Medmont DACP testing within 50 days. Repeatability coefficients for prebleach scotopic sensitivity to long wavelength (red, 625 nm) and short wavelength (cyan, 505 nm) were 5.9 dB and 7.2 dB, respectively. The DA curve-derived repeatability coefficients for cone threshold was 3.9 dB, final threshold 5.3 dB, with an R value of 0.075 decades/min, rod intercept time 7.6 minutes, and RITslope 0.54 min/degree. Conclusions:This study establishes repeatability coefficients for scotopic thresholds and multiple DA parameters obtained with the Medmont DACP in patients with age-related macular degeneration. These repeatability coefficients will serve as the basis for determining clinically meaningful change in rod function in future clinical trials. Translational Relevance:Measures of repeatability parameters of scotopic thresholds and DA are essential to the accurate interpretation of results in future studies and trials using these measures.
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