title: Interphotoreceptor retinoid-binding protein as the physiologically relevant carrier of 11-cis-retinol in the cone visual cycle.
abstract: Cones function in constant light and are responsible for mediating daytime human vision. Like rods, cones use the photosensitive molecule 11-cis-retinal to detect light, and in constant illumination, a continuous supply of 11-cis-retinal is needed. A retina visual cycle is thought to provide a privileged supply of 11-cis-retinal to cones by using 11-cis-retinol generated in Müller cells. In the cycle, 11-cis-retinol is transported from Müller cells to cone inner segments, where it is oxidized to 11-cis-retinal. This oxidation step is only performed in cones, thus rendering the cycle cone-specific. Interphotoreceptor retinoid-binding protein (IRBP) is a retinoid-binding protein in the subretinal space that binds 11-cis-retinol endogenously. Cones in Irbp(-/-) mice are retinoid-deficient under photopic conditions, and it is possible that 11-cis-retinol supplies are disrupted in the absence of IRBP. We tested the hypothesis that IRBP facilitates the delivery of 11-cis-retinol to cones by preserving the isomeric state of 11-cis-retinol in light. With electrophysiology, we show that the cone-like photoreceptors of Nrl(-/-) mice use the cone visual cycle similarly to wild-type cones. Then, using oxidation assays in isolated Nrl(-/-)Rpe65(-/-) retinas, we show that IRBP delivers 11-cis-retinol for oxidation in cones and improves the efficiency of the oxidation reaction. Finally, we show that IRBP protects the isomeric state of 11-cis-retinol in the presence of light. Together, these findings suggest that IRBP plays an important role in the delivery of 11-cis-retinol to cones and can facilitate cone function in the presence of light.
authors: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29403, USA. parkerry@musc.edu
authors: Ryan
authors: R
authors: Parker
authors: Jin-Shan
authors: JS
authors: Wang
authors: Vladimir J
authors: VJ
authors: Kefalov
authors: Rosalie K
authors: RK
authors: Crouch
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D008027:Light; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D012176:Retinoids / Q000737:chemistry / Q000378:metabolism; D012177:Retinol-Binding Proteins / Q000378:metabolism*; D014785:Vision, Ocular / Q000502:physiology; D014801:Vitamin A / Q000378:metabolism*; D019745:cis-trans-Isomerases; D000099214:Retinol-Binding Proteins, Interstitial; D000099178:Retinoid Isomerohydrolase
chemical_list: D002352:Carrier Proteins; D005136:Eye Proteins; D012176:Retinoids; D012177:Retinol-Binding Proteins; D014801:Vitamin A; D019745:cis-trans-Isomerases; D000099214:Retinol-Binding Proteins, Interstitial; D000099178:Retinoid Isomerohydrolase