Interphotoreceptor retinoid-binding protein as the physiologically relevant carrier of 11-cis-retinol in the cone visual cycle.
Interphotoreceptor retinoid-binding protein as the physiologically relevant carrier of 11-cis-retinol in the cone visual cycle.
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DOI：
10.1523/jneurosci.3722-10.2011
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发表时间：
2011-03-23
期刊：
影响因子：
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通讯作者：
Crouch RK
中科院分区：
文献类型：
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作者：
Parker R;Wang JS;Kefalov VJ;Crouch RK
Cones function in constant light and are responsible for mediating daytime human vision. Like rods, cones utilize the photo-sensitive 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 utilizing 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 carried out in cones, thus rendering the cycle cone-specific. IRBP is a retinoid-binding protein in the sub-retinal 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 utilize 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.
