RPE65 is essential for the function of cone photoreceptors in NRL-deficient mice
RPE65 is essential for the function of cone photoreceptors in NRL-deficient mice
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DOI：
10.1167/iovs.06-0652
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发表时间：
2007-02-01
影响因子：
4.4
通讯作者：
Seeliger, Mathias W.
中科院分区：
文献类型：
--
作者：
Wenzel, Andreas;von Lintig, Johannes;Seeliger, Mathias W.
目的。视锥细胞中的光转导是由视色素的漂白启动的，视色素由蛋白质成分视锥细胞视蛋白和维生素 A 衍生物 - 11-顺式视黄醛组成。关于视锥细胞 11-顺式视网膜的来源知之甚少。在当前的研究中，使用神经视网膜亮氨酸拉链缺陷（Nrl（-/-））和杆视蛋白（Rho（-/-））缺陷的小鼠（这两种被描述为具有“仅视锥细胞”视网膜的小鼠模型）来分析视锥细胞的类维生素A代谢。此外，将这些小鼠与视网膜色素上皮蛋白65(Rpe65(-/-))缺陷小鼠交配以研究RPE65的作用。方法。使用形态学、蛋白质印迹分析、免疫组织化学、视网膜电图 (ERG) 和 HPLC 进行类视黄醇分析来分析小鼠。结果。与野生型小鼠相比，Nrl(-/-)小鼠的视网膜中RPE65和细胞视黄醛结合蛋白(CRALBP)水平升高，表明这两种蛋白对于视锥细胞的类视黄醇代谢具有特殊作用。在Nrl(-/-)小鼠中，不同类视黄醇种类的存在比例与野生型相似。 Nrl(-/-)和Rho(-/-)小鼠中RPE65的消除导致11-顺式视黄醛的缺失，但增加了类视黄醇的总含量，其中视黄酯代表了最丰富的类视黄醇种类。在缺乏 RPE65 的情况下，Nrl(-/-) 小鼠的视网膜敏感性下降了千分之一。结论。数据显示，之前被证明对视杆细胞功能至关重要的 RPE65 对于视锥细胞的 11-顺式视黄醛的产生也是必不可少的，从而对于视锥细胞功能也是必不可少的。
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.