Thompson Debra A, Gal Andreas
Departments of Ophthalmology and Visual Sciences, and Biological Chemistry, University of Michigan Medical School, Ann Arbor, Mich., USA.
Dev Ophthalmol. 2003;37:141-54. doi: 10.1159/000072044.
The metabolism of vitamin A and cycling of retinoids between the retinal pigment epithelium (RPE) and the neural retina is a complex process involving a specialized enzymes and proteins. Mutations in a number of the corresponding genes are responsible for various forms of inherited retinal dystrophy and dysfunction. Research into the causes and treatment of retinal diseases resulting from defects in vitamin A metabolism is currently the subject of intense interest, since disorders affecting RPE function are, in principle, more accessible to therapeutic intervention than those affecting the proteins of the photoreceptor cells. In this chapter we present an overview of the visual cycle, as well as the function of the known RPE genes involved in the conversion of vitamin A (all-trans retinol) to 11-cis retinal, the chromophore of the visual pigments. We describe the identification of disease-associated mutations in this set of genes in patients with diverse forms of retinal dystrophy and dysfunction, as well as the spectrum of mutations and associated phenotypes. We also discuss the results of recent studies using animal models of the disease caused by mutations of RPE65. On the basis of these advances, it is hoped that patients with defects in RPE vitamin A metabolism will be among the first successfully treated by targeted therapies likely to become available in the near future.
维生素A的代谢以及视黄醛在视网膜色素上皮（RPE）和神经视网膜之间的循环是一个复杂的过程，涉及多种特殊的酶和蛋白质。许多相应基因的突变会导致各种形式的遗传性视网膜营养不良和功能障碍。由于影响RPE功能的疾病原则上比影响光感受器细胞蛋白质的疾病更易于进行治疗干预，因此对因维生素A代谢缺陷导致的视网膜疾病的病因和治疗研究目前备受关注。在本章中，我们将概述视觉循环，以及已知的参与将维生素A（全反式视黄醇）转化为视黄醛（视觉色素的发色团）的RPE基因的功能。我们将描述在患有各种形式视网膜营养不良和功能障碍的患者中，这组基因中与疾病相关的突变鉴定，以及突变谱和相关表型。我们还将讨论使用由RPE65突变引起的疾病动物模型的最新研究结果。基于这些进展，希望RPE维生素A代谢缺陷的患者将成为最早通过不久的将来可能可用的靶向治疗成功治疗的患者之一。
