Mutations in the genes necessary for the metabolism of vitamin A (all-trans retinol) and cycling of retinoids between the photoreceptors and retinal pigment epithelium (RPE) (the visual cycle) have recently emerged as an important class of genetic defects responsible for retinal dystrophies and dysfunctions. Research into the causes and treatment of diseases resulting from defects in retinal vitamin A metabolism is currently the subject of intense interest, since disorders affecting the RPE are, in principle, more accessible to therapeutic intervention than those affecting the proteins of photoreceptor cells. This chapter presents an overview of the visual cycle, as well as the function of the RPE genes involved in the conversion of vitamin A to 11-cis retinal, the chromophore of the visual pigments. The identification of disease-causing mutations in this group of genes is described as well as the associated phenotypes that range from stationary night blindness to childhood-onset severe visual handicap. Consideration is also given to alternative genetic paradigms potentially relevant to defects in vitamin A metabolism, including a discussion of the relationship of this pathway to age-related macular degeneration, a non-Mendelian disease of late onset. Finally, progress and prospects for targeted therapeutic intervention in vitamin A metabolism are presented, including retinoid and gene replacement therapy. On the basis of early successes in animal models, and plans underway for Phase I/II clinical trials, it is hoped that the near future will bring effective therapies for many retinal dystrophy patients with defects in vitamin A metabolism.

中文翻译：

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视网膜色素上皮中的维生素A代谢：基因，突变和疾病。

维生素A（全反式视黄醇）代谢和类维生素A在感光体和视网膜色素上皮（RPE）之间循环（视觉周期）所必需的基因突变最近已成为引起视网膜营养不良的重要遗传缺陷类别。和功能障碍。目前，对视网膜维生素A代谢缺陷导致的疾病的原因和治疗方法的研究引起了人们的极大兴趣，因为从原则上说，影响RPE的疾病比影响感光细胞蛋白的疾病更易于治疗。本章概述了视觉周期，以及RPE基因在维生素A向11-顺式视网膜（视觉色素的发色团）转化中的功能。描述了在这组基因中引起疾病​​的突变的鉴定，以及相关的表型，包括从固定夜盲症到儿童期严重视觉障碍的范围。还考虑了可能与维生素A代谢缺陷相关的替代遗传学范式，包括对该途径与年龄相关性黄斑变性（一种迟发性非孟德尔疾病）的关系的讨论。最后，介绍了针对维生素A代谢的靶向治疗干预的进展和前景，包括类维生素A和基因替代治疗。基于动物模型的早期成功，并计划进行I / II期临床试验，希望不久的将来将为许多维生素A代谢缺陷的视网膜营养不良患者带来有效的疗法。