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

Aleksander Tworak(University of California, Irvine), Alexander V. Kolesnikov(University of California, Irvine), John D. Hong(University of California, Irvine), Elliot H. Choi(University of California, Irvine), Jennings Luu(University of California, Irvine), Grażyna Palczewska(University of California, Irvine), Zhiqian Dong(University of California, Irvine), Dominik Lewandowski(University of California, Irvine), Matthew J. Brooks(National Institutes of Health), Laura Campello(National Institutes of Health), Anand Swaroop(National Institutes of Health), Philip D. Kiser(University of California, Irvine), Vladimir J. Kefalov(University of California, Irvine), Krzysztof Palczewski(University of California, Irvine)
Cell Reports
August 1, 2023
10.1016/j.celrep.2023.112982
Cited by 38Open Access
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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.

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