Non-photopic and photopic visual cycles differentially regulate immediate, early and late-phases of cone photoreceptor-mediated vision

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Title: Non-photopic and photopic visual cycles differentially regulate immediate, early and late-phases of cone photoreceptor-mediated vision
Other Titles: Chemical Biology of Visual Cycles Enabling Cone Vision
Authors: Ward, RebeccaKaylor, Joanna J.Cobice, Diego F.Pepe, Dionissia A.McGarrigle, Eoghan M.Kennedy, Breandánet al.
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Date: 8-May-2020
Online since: 2020-08-25T13:37:01Z
Abstract: Cone photoreceptors in the retina enable vision over a wide range of light intensities. However, the processes enabling cone vision in bright light (i.e. photopic vision) are not adequately understood. Chromophore regeneration of cone photopigments may require the retinal pigment epithelium (RPE) and/or retinal Müller glia. In the RPE, isomerization of all-trans-retinyl esters (atRE) to 11-cis-retinol (11cROL) is mediated by the retinoid isomerohydrolase Rpe65. A putative alternative retinoid isomerase, dihydroceramide desaturase-1 (DES1), is expressed in RPE and Müller cells. The retinol-isomerase activities of Rpe65 and Des1 are inhibited by emixustat and fenretinide, respectively. Here, we tested the effects of these visual cycle inhibitors on immediate, early and late phases of cone photopic vision. In zebrafish larvae raised under cyclic light conditions, fenretinide impaired late cone photopic vision, whereas emixustat-treated zebrafish unexpectedly had normal vision. In contrast, emixustat-treated larvae raised under extensive dark-adaption displayed significantly attenuated immediate photopic vision concomitant with significantly reduced 11-cis-retinaldehyde (11cRAL). Following 30 minutes of light, early photopic vision recovered, despite 11cRAL levels remaining significantly reduced. Defects in immediate cone photopic vision were rescued in emixustat- or fenretinide-treated larvae following exogenous 9-cis-retinaldehyde (9cRAL) supplementation. Genetic knockout of Des1 (degs1) or retinaldehyde-binding protein 1b (rlbp1b) did not eliminate photopic vision in zebrafish. Our findings define molecular and temporal requirements of the non-photopic or photopic visual cycles for mediating vision in bright light.
Funding Details: European Commission Horizon 2020
Irish Research Council
metadata.dc.description.othersponsorship: National Institutes of Health
Type of material: Journal Article
Publisher: American Society for Biochemistry and Molecular Biology
Journal: Journal of Chemistry Biology
Volume: 295
Issue: 19
Start page: 6482
End page: 6497
Copyright (published version): 2020 the Authors
Keywords: Visual cycleZebrafishRetinaVisionPharmacologyCone-based visual behaviourRpe65Vitamin A
DOI: 10.1074/jbc.RA119.011374
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
Biomolecular and Biomedical Science Research Collection
Chemistry Research Collection

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