Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle
Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle
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DOI：
10.1038/3813
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发表时间：
1998-12-01
期刊：
影响因子：
30.8
通讯作者：
Pfeifer, K
中科院分区：
文献类型：
--
作者：
Redmond, TM;Yu, S;Pfeifer, K
RPE 65突变可导致出生或儿童早期严重失明，RPE 65蛋白与视网膜色素上皮（RPE）维生素A代谢相关。这里.我们发现Rpe 65缺陷小鼠表现出视网膜生理学和生物化学的变化。与Rpe 65（+/+）和Rpe 65（+/-）小鼠相比，Rpe 65（-/-）小鼠的视杆细胞光感受器外节盘紊乱。通过视网膜电图测量，Rpe 65（-/-）小鼠的视杆细胞功能消失，但视锥细胞功能仍然存在。Rpe 65（-/-）小鼠缺乏视紫红质，但不缺乏视蛋白脱辅基蛋白。此外，全反式视黄酯在Rpe 65（-/-）小鼠的RPE中过度积累，而11-顺式视黄酯不存在。因此，尽管视锥色素再生可能依赖于单独的途径，但基于RPE的全反式视黄酯代谢为11-顺式-视黄醛的破坏似乎是Rpe 65（-/-）表型的基础。
Mutation of RPE65 can cause severe blindness from birth or early childhood, and RPE65 protein is associated with retinal pigment epithelium (RPE) vitamin A metabolism. Here. we show that Rpe65-deficient mice exhibit changes in retinal physiology and biochemistry. Outer segment discs of rod photoreceptors in Rpe65(-/-) mice are disorganized compared with those of Rpe65(+/+) and Rpe65(+/-) mice. Rod function, as measured by electroretinography, is abolished in Rpe65(-/-) mice, although cone function remains. Rpe65(-/-) mice lack rhodopsin, but not opsin apoprotein. Furthermore, all-trans-retinyl esters over-accumulate in the RPE of Rpe65(-/-) mice, whereas 11-cis-retinyl esters are absent. Disruption of the RPE-based metabolism of all-trans-retinyl esters to 11-cis-retinal thus appears to underlie the Rpe65(-/-) phenotype, although cone pigment regeneration may be dependent on a separate pathway.