Light-Driven Regeneration of Cone Visual Pigments through a Mechanism Involving RGR Opsin in Müller Glial Cells

• Published in: Neuron (Cambridge, Mass.) Vol. 102; no. 6; pp. 1172 - 1183.e5
• Main Authors: Morshedian, Ala, Kaylor, Joanna J., Ng, Sze Yin, Tsan, Avian, Frederiksen, Rikard, Xu, Tongzhou, Yuan, Lily, Sampath, Alapakkam P., Radu, Roxana A., Fain, Gordon L., Travis, Gabriel H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19-06-2019; Elsevier Limited
• Subjects: 2-Aminoadipic Acid - pharmacology; Alcohol Oxidoreductases - metabolism; Alcohol Oxidoreductases - radiation effects; Animals; Cones; Dehydrogenases; Ependymoglial Cells - drug effects; Ependymoglial Cells - metabolism; Ependymoglial Cells - radiation effects; Epithelium; Excitatory Amino Acid Antagonists - pharmacology; Eye Proteins - genetics; Eye Proteins - metabolism; Eye Proteins - radiation effects; Glial cells; Light; Mammals; Mice; Mice, Knockout; Mutation; Photopigments; Photoreceptors; Photoresponse; Proteins; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Receptors, G-Protein-Coupled - radiation effects; Regeneration; Retina; Retinal Cone Photoreceptor Cells - metabolism; Retinal Cone Photoreceptor Cells - radiation effects; Retinal pigment epithelium; Retinal Pigments - metabolism; Retinal Pigments - radiation effects; Retinol dehydrogenase; Rhodopsin; Rods; Vitamin A; Vitamin A - metabolism
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2019.04.004

While rods in the mammalian retina regenerate rhodopsin through a well-characterized pathway in cells of the retinal pigment epithelium (RPE), cone visual pigments are thought to regenerate in part through an additional pathway in Müller cells of the neural retina. The proteins comprising this intrinsic retinal visual cycle are unknown. Here, we show that RGR opsin and retinol dehydrogenase-10 (Rdh10) convert all-trans-retinol to 11-cis-retinol during exposure to visible light. Isolated retinas from Rgr+/+ and Rgr−/− mice were exposed to continuous light, and cone photoresponses were recorded. Cones in Rgr−/− retinas lost sensitivity at a faster rate than cones in Rgr+/+ retinas. A similar effect was seen in Rgr+/+ retinas following treatment with the glial cell toxin, α-aminoadipic acid. These results show that RGR opsin is a critical component of the Müller cell visual cycle and that regeneration of cone visual pigment can be driven by light.
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•RGR opsin and Rdh10 convert atROL to 11cROL upon exposure to visible light•Normal mouse retinas maintain cone sensitivity during exposure to background light•Rgr−/− mouse retinas progressively lose cone sensitivity during light exposure•Treatment of normal mouse retinas with a Müller cell toxin replicates the Rgr−/− phenotype
Morshedian et al. report that RGR opsin in Müller cells functions to regenerate cone visual pigments during light exposure and is the likely isomerase of the intrinsic retinal visual cycle. RGR opsin is required to maintain cone sensitivity during sustained light exposure.