SEARCHOTHERophthalmology, retina

other·ophthalmology, retina, preclinical research, biomedical research·PMC10530494

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

Cell reports · 14 authors, 10 centres

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TL;DR

This preclinical study used cell-specific gene reactivation in mice to show that both the retinal pigment epithelium (RPE) and a specialized subset of Müller glia contribute to rapid visual pigment recycling via the photoisomerase RGR, supporting both rod and cone photoreceptor function in light.

Full summary

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This preclinical study employed a cell-specific gene reactivation approach in mice to investigate the kinetics and relative contributions of the retinal G-protein-coupled receptor (RGR) expressed in the retinal pigment epithelium (RPE) and specialized Müller glia to visual pigment recycling. Electroretinographic measurements revealed that RGR pools in both cell types support scotopic (rod-mediated) and photopic (cone-mediated) function. The authors demonstrated that 11-cis-retinal formed via RGR photoisomerization is rapidly hydrolyzed, consistent with its role in a fast photic visual cycle. The study shows RGR acts as a sink for all-trans-retinal under sustained light and supports rapid chromophore regeneration. Limitations include a primary focus on cone function and species-specific differences in Müller glia fraction and transcriptomes. The findings suggest RGR in the RPE and Müller glia are non-redundant, with RPE RGR providing greater support for cone sensitivity during prolonged light exposure and dark adaptation.

STUDY TYPE

other

SPECIALTY

ophthalmology

SUMMARISED BY

AI pipeline

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ORIGINAL PAPER

PMC10530494

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

Cell reports

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ABSTRACT

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.

CITATION EXPORT

Aleksander Tworak, Alexander V. Kolesnikov, John D. Hong et al.. Rapid RGR-dependent visual pigment recycling is mediated by the RPE and specialized Müller glia. Cell reports. (2023). https://doi.org/10.1016/j.celrep.2023.112982

AUTHORS

14 · 10 CENTRES

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

1Department of Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA 92697, USA
2Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA
3Polgenix, Inc., Department of Medical Devices, Cleveland, OH 44106, USA
4Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
5Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA 92697, USA
6Department of Clinical Pharmacy Practice, University of California, Irvine, Irvine, CA 92697, USA
7Research Service, VA Long Beach Healthcare System, Long Beach, CA 90822, USA
8Department of Chemistry, University of California, Irvine, Irvine, CA 92697, USA
9Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697, USA
10Lead contact