RPE65 is essential for the function of cone photoreceptors in NRL-deficient mice.
PURPOSE: Phototransduction in cones is initiated by the bleaching of their visual pigment, which comprises a protein component-cone opsin-and a vitamin A derivative-11-cis retinal. Little is known about the source of 11-cis retinal for cones. In the current study, neural retina leucine zipper-deficient (Nrl(-/-)) and rod opsin (Rho(-/-))-deficient mice were used, two mouse models that have been described as having a "cone-only" retina, to analyze the retinoid metabolism of cones. In addition, these mice were bred to retinal pigment epithelial protein 65 (Rpe65(-/-))-deficient mice to study the role of RPE65. METHODS: Mice were analyzed using morphology, Western blot analysis, immunohistochemistry, electroretinography (ERG), and retinoid profiling by HPLC. RESULTS: In comparison to wild-type mice, the retina of Nrl(-/-) mice contained elevated levels of RPE65 and cellular retinaldehyde-binding protein (CRALBP), suggesting a particular role of these two proteins for the retinoid metabolism of cones. In Nrl(-/-) mice, different retinoid species were present in proportions similar to wild type. Ablation of RPE65 in Nrl(-/-) and Rho(-/-) mice led to the absence of 11-cis retinal, but increased the total retinoid content, with retinyl esters representing the most abundant retinoid species. In the absence of RPE65, retinal sensitivity in Nrl(-/-) mice dropped by a factor of a thousand. CONCLUSIONS: The data show that RPE65, previously shown to be essential for rod function, is also indispensable for the production of 11-cis retinal for cones and thus for cone function.
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CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y GENE-Y GENE-Y GENE-N GENE-N GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-N GENE-N GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-N GENE-Y
retinoid 11-cis retinal retinoid retinyl esters retinoid vitamin A 11-cis retinal 11-cis retinal 11-cis retinal leucine retinoid retinoid retinaldehyde retinoid Nrl RPE65 Nrl Rho cone opsin RPE65 Nrl RPE65 neural retina leucine zipper Nrl rod opsin Rho retinal pigment epithelial protein 65 Rpe65 RPE65 Nrl RPE65 cellular retinaldehyde-binding protein CRALBP RPE65 photoreceptors NRL