Redmond T M, Yu S, Lee E, Bok D, Hamasaki D, Chen N, Goletz P, Ma J X, Crouch R K, Pfeifer K
Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Genet. 1998 Dec;20(4):344-51. doi: 10.1038/3813.
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.
RPE65基因突变可导致出生时或幼儿期严重失明，且RPE65蛋白与视网膜色素上皮（RPE）的维生素A代谢相关。在此，我们表明Rpe65基因缺陷小鼠在视网膜生理和生化方面出现变化。与Rpe65+/+和Rpe65+/-小鼠相比，Rpe65-/-小鼠视杆光感受器的外节盘排列紊乱。通过视网膜电图测量，Rpe65-/-小鼠的视杆功能丧失，尽管视锥功能尚存。Rpe65-/-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Rpe65-/-小鼠的RPE中过度积累，而11-顺式视黄酯缺失。因此，全反式视黄酯向11-顺式视黄醛的基于RPE的代谢中断似乎是Rpe65-/-表型的基础，尽管视锥色素再生可能依赖于一条独立的途径。
