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

Aleksander Tworak; Alexander V Kolesnikov; John D Hong; Elliot H Choi; Jennings C Luu; Grazyna Palczewska; Zhiqian Dong; Dominik Lewandowski; Matthew J Brooks; Laura Campello; Anand Swaroop; Philip D Kiser; Vladimir J Kefalov; Krzysztof Palczewski

doi:10.1016/j.celrep.2023.112982

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.

Affiliations

¹ Department of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: atworak@uci.edu.
² Department of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA 92697, USA.
³ Department of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA 92697, USA; Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA.
⁴ Department of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA 92697, USA; Polgenix, Inc., Department of Medical Devices, Cleveland, OH 44106, USA.
⁵ Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁶ Department of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA 92697, USA; Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA 92697, USA; Department of Clinical Pharmacy Practice, University of California, Irvine, Irvine, CA 92697, USA; Research Service, VA Long Beach Healthcare System, Long Beach, CA 90822, USA.
⁷ Department of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA 92697, USA; Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA 92697, USA.
⁸ Department of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA 92697, USA; Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA 92697, USA; Department of Chemistry, University of California, Irvine, Irvine, CA 92697, USA; Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: kpalczew@uci.edu.

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

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

Authors

Affiliations

Abstract

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MeSH terms

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