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

Ala Morshedian; Joanna J Kaylor; Sze Yin Ng; Avian Tsan; Rikard Frederiksen; Tongzhou Xu; Lily Yuan; Alapakkam P Sampath; Roxana A Radu; Gordon L Fain; Gabriel H Travis

doi:10.1016/j.neuron.2019.04.004

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

Neuron. 2019 Jun 19;102(6):1172-1183.e5. doi: 10.1016/j.neuron.2019.04.004. Epub 2019 May 2.

Authors

Affiliations

¹ Stein Eye Institute and Department of Ophthalmology, University of California, Los Angeles, Los Angeles, CA, USA.
² Stein Eye Institute and Department of Ophthalmology, University of California, Los Angeles, Los Angeles, CA, USA; Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
³ Stein Eye Institute and Department of Ophthalmology, University of California, Los Angeles, Los Angeles, CA, USA; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: [email protected].

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

2-Aminoadipic Acid / pharmacology
Alcohol Oxidoreductases / metabolism
Alcohol Oxidoreductases / radiation effects
Animals
Ependymoglial Cells / drug effects
Ependymoglial Cells / metabolism*
Ependymoglial Cells / radiation effects
Excitatory Amino Acid Antagonists / pharmacology
Eye Proteins / genetics*
Eye Proteins / metabolism
Eye Proteins / radiation effects
Light
Mice
Mice, Knockout
Receptors, G-Protein-Coupled / genetics*
Receptors, G-Protein-Coupled / metabolism
Receptors, G-Protein-Coupled / radiation effects
Retinal Cone Photoreceptor Cells / metabolism*
Retinal Cone Photoreceptor Cells / radiation effects
Retinal Pigments / metabolism*
Retinal Pigments / radiation effects
Vitamin A / metabolism

Substances

Excitatory Amino Acid Antagonists
Eye Proteins
G protein-coupled receptor RGR
Receptors, G-Protein-Coupled
Retinal Pigments
Vitamin A
2-Aminoadipic Acid
Alcohol Oxidoreductases
trans-retinol dehydrogenase

Abstract

Publication types

MeSH terms

Substances

Grants and funding