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

Cell Reports (Aug 2023)

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

Affiliations

Aleksander Tworak: Department of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA 92697, USA; Corresponding author
Alexander V. Kolesnikov: Department of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA 92697, USA
John D. Hong: Department of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA 92697, USA
Elliot H. Choi: Department of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA 92697, USA
Jennings C. Luu: 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
Grazyna Palczewska: 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
Zhiqian Dong: Department of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA 92697, USA
Dominik Lewandowski: Department of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA 92697, USA
Matthew J. Brooks: Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
Laura Campello: Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
Anand Swaroop: Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
Philip D. Kiser: 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
Vladimir J. Kefalov: 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
Krzysztof Palczewski: 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; Corresponding author

Journal volume & issue: Vol. 42, no. 8
p. 112982

Abstract

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Summary: 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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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