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

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  • Additional Information
    • Source:
      Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE
    • Publication Information:
      Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology
      Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology
    • Subject Terms:
      Color Vision*; Ependymoglial Cells/*metabolism ; Retinal Cone Photoreceptor Cells/*metabolism ; Zebrafish/*metabolism; Animals ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Ependymoglial Cells/cytology ; Fatty Acid Desaturases/genetics ; Fatty Acid Desaturases/metabolism ; Gene Deletion ; Retinal Cone Photoreceptor Cells/cytology ; Vitamin A/genetics ; Vitamin A/metabolism ; Zebrafish/genetics ; cis-trans-Isomerases/genetics ; cis-trans-Isomerases/metabolism
    • 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 to 11- cis -retinol 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, while the emixustat-treated zebrafish unexpectedly had normal vision. In contrast, emixustat-treated larvae raised under extensive dark-adaptation displayed significantly attenuated immediate photopic vision concomitant with significantly reduced 11- cis -retinaldehyde (11cRAL). Following 30 min of light, early photopic vision was 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 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 nonphotopic or photopic visual cycles for mediating vision in bright light.
      (© 2020 Ward et al.)
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    • Grant Information:
      P30 EY000331 United States EY NEI NIH HHS; R01 EY024379 United States EY NEI NIH HHS
    • Contributed Indexing:
      Keywords: Rpe65; chemical biology; cone-based visual behavior; pharmacology; retina; vision; visual cycle; vitamin A; zebrafish
    • Accession Number:
      0 (11-cis-retinal-binding protein)
      0 (Carrier Proteins)
      11103-57-4 (Vitamin A)
      EC 1.14.19.- (Fatty Acid Desaturases)
      EC 3.1.1.64 (retinoid isomerohydrolase)
      EC 5.2.- (cis-trans-Isomerases)
    • Publication Date:
      Date Created: 20200403 Date Completed: 20201223 Latest Revision: 20210508
    • Publication Date:
      20240829
    • Accession Number:
      PMC7212626
    • Accession Number:
      10.1074/jbc.RA119.011374
    • Accession Number:
      32238432