Rapid RGR-dependent visual pigment recycling is mediated by the RPE and specialized Müller glia

Cell Rep. 2023 Aug 29;42(8):112982. doi: 10.1016/j.celrep.2023.112982. Epub 2023 Aug 15.

Abstract

In daylight, demand for visual chromophore (11-cis-retinal) exceeds supply by the classical visual cycle. This shortfall is compensated, in part, by the retinal G-protein-coupled receptor (RGR) photoisomerase, which is expressed in both the retinal pigment epithelium (RPE) and in Müller cells. The relative contributions of these two cellular pools of RGR to the maintenance of photoreceptor light responses are not known. Here, we use a cell-specific gene reactivation approach to elucidate the kinetics of RGR-mediated recovery of photoreceptor responses following light exposure. Electroretinographic measurements in mice with RGR expression limited to either cell type reveal that the RPE and a specialized subset of Müller glia contribute both to scotopic and photopic function. We demonstrate that 11-cis-retinal formed through photoisomerization is rapidly hydrolyzed, consistent with its role in a rapid visual pigment regeneration process. Our study shows that RGR provides a pan-retinal sink for all-trans-retinal released under sustained light conditions and supports rapid chromophore regeneration through the photic visual cycle.

Keywords: 11-cis-retinal; CP: Cell biology; CP: Neuroscience; Müller cells; chromophore; cone opsin; photic visual cycle; photoisomerization; retina; retinal pigmented epithelium; vision; visual cycle.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Mice
  • Neuroglia / metabolism
  • Receptors, G-Protein-Coupled / metabolism
  • Retinal Cone Photoreceptor Cells / metabolism
  • Retinal Pigment Epithelium* / metabolism
  • Retinal Pigments / metabolism
  • Retinaldehyde* / metabolism

Substances

  • Retinaldehyde
  • Retinal Pigments
  • Receptors, G-Protein-Coupled