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Publication : Interphotoreceptor retinoid-binding protein as the physiologically relevant carrier of 11-cis-retinol in the cone visual cycle.

First Author  Parker R Year  2011
Journal  J Neurosci Volume  31
Issue  12 Pages  4714-9
PubMed ID  21430170 Mgi Jnum  J:309865
Mgi Id  MGI:6708186 Doi  10.1523/JNEUROSCI.3722-10.2011
Citation  Parker R, et al. (2011) Interphotoreceptor retinoid-binding protein as the physiologically relevant carrier of 11-cis-retinol in the cone visual cycle. J Neurosci 31(12):4714-9
abstractText  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 Muller cells. In the cycle, 11-cis-retinol is transported from Muller 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.
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