Non-photopic and photopic visual cycles differentially regulate immediate, early and late-phases of cone photoreceptor-mediated vision
| Autor: | Susan E. Brockerhoff, Gabriel H. Travis, Joanna J. Kaylor, Eoghan M. McGarrigle, Diego Cobice, Dionissia A. Pepe, Breandán N. Kennedy, James B. Hurley, Rebecca Ward |
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| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
Retina Retinal pigment epithelium genetic structures Retinal Biology eye diseases Cell biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine.anatomical_structure chemistry RPE65 medicine Photopigment sense organs Muller glia 030217 neurology & neurosurgery 030304 developmental biology Photopic vision Visual phototransduction |
| DOI: | 10.1101/2020.02.15.950915 |
| Popis: | 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. An 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 concomitantly 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 degs1 or retinaldehyde-binding protein 1b (rlbp1b) revealed that neither are required for photopic vision in zebrafish. Our findings define the molecular and temporal requirements of the non-photopic and photopic visual cycles for mediating vision in bright light. |
| Databáze: | OpenAIRE |
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