cis Retinol oxidation regulates photoreceptor access to the retina visual cycle and cone pigment regeneration

Shinya Sato, Vladimir J. Kefalov

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Key points: This study explores the nature of the cis retinol that Müller cells in the retina provide to cones for the regeneration of their visual pigment. We report that the retina visual cycle provides cones exclusively with 11-cis chromophore in both salamander and mouse and show that this selectivity is dependent on the 11-cis-specific cellular retinaldehyde binding protein (CRALBP) present in Müller cells. Even though salamander blue cones and green rods share the same visual pigment, only blue cones but not green rods are able to dark-adapt in the retina following a bleach and to use exogenous 9-cis retinol for pigment regeneration, suggesting that access to the retina visual cycle is cone-specific and pigment-independent. Our results show that the retina produces 11-cis retinol that can be oxidized and used for pigment regeneration and dark adaptation selectively in cones and not in rods. Abstract: Chromophore supply by the retinal Müller cells (retina visual cycle) supports the efficient pigment regeneration required for cone photoreceptor function in bright light. Surprisingly, a large fraction of the chromophore produced by dihydroceramide desaturase-1, the putative all-trans retinol isomerase in Müller cells, appears to be 9-cis retinol. In contrast, the canonical retinal pigment epithelium (RPE) visual cycle produces exclusively 11-cis retinal. Here, we used the different absorption spectra of 9-cis and 11-cis pigments to identify the isoform of the chromophore produced by the visual cycle of the intact retina. We found that the spectral sensitivity of salamander and mouse cones dark-adapted in the isolated retina (with only the retina visual cycle) was similar to that of cones dark-adapted in the intact eye (with both the RPE and retina visual cycles) and consistent with pure 11-cis pigment composition. However, in mice lacking the cellular retinaldehyde binding protein (CRALBP), cone spectral sensitivity contained a substantial 9-cis component. Thus, the retina visual cycle provides cones exclusively with 11-cis chromophore and this process is mediated by the 11-cis selective CRALBP in Müller cells. Finally, despite sharing the same pigment, salamander blue cones, but not green rods, recovered their sensitivity in the isolated retina. Exogenous 9-cis retinol produced robust sensitivity recovery in bleached red and blue cones but not in red and green rods, suggesting that cis retinol oxidation restricts access to the retina visual cycle to cones.

Original languageEnglish
Pages (from-to)6753-6765
Number of pages13
JournalJournal of Physiology
Volume594
Issue number22
DOIs
StatePublished - Nov 15 2016

Keywords

  • CRALBP
  • cone photoreceptors
  • dark adaptation
  • retina
  • retinol dehydrogenase
  • visual cycle

Fingerprint

Dive into the research topics of 'cis Retinol oxidation regulates photoreceptor access to the retina visual cycle and cone pigment regeneration'. Together they form a unique fingerprint.

Cite this