PUBLICATION
Non-photopic and photopic visual cycles differentially regulate immediate, early and late-phases of cone photoreceptor-mediated vision
- Authors
- Ward, R., Kaylor, J.J., Cobice, D.F., Pepe, D.A., McGarrigle, E.M., Brockerhoff, S.E., Hurley, J.B., Travis, G.H., Kennedy, B.N.
- ID
- ZDB-PUB-200403-235
- Date
- 2020
- Source
- The Journal of biological chemistry 295(19): 6482-6497 (Journal)
- Registered Authors
- Brockerhoff, Susan, Hurley, James B., Kennedy, Breandan N.
- Keywords
- Chemical Biology, Cone-Based Visual Behaviour, Rpe65, Visual Cycle, Zebrafish, pharmacology, retina, vision, vitamin A, zebrafish
- MeSH Terms
-
- Animals
- Carrier Proteins/genetics
- Carrier Proteins/metabolism
- Color Vision*
- Ependymoglial Cells/cytology
- Ependymoglial Cells/metabolism*
- Fatty Acid Desaturases/genetics
- Fatty Acid Desaturases/metabolism
- Gene Deletion
- Retinal Cone Photoreceptor Cells/cytology
- Retinal Cone Photoreceptor Cells/metabolism*
- Vitamin A/genetics
- Vitamin A/metabolism
- Zebrafish/genetics
- Zebrafish/metabolism*
- cis-trans-Isomerases/genetics
- cis-trans-Isomerases/metabolism
- PubMed
- 32238432 Full text @ J. Biol. Chem.
Citation
Ward, R., Kaylor, J.J., Cobice, D.F., Pepe, D.A., McGarrigle, E.M., Brockerhoff, S.E., Hurley, J.B., Travis, G.H., Kennedy, B.N. (2020) Non-photopic and photopic visual cycles differentially regulate immediate, early and late-phases of cone photoreceptor-mediated vision. The Journal of biological chemistry. 295(19):6482-6497.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping