Charbel Issa P, Groppe M, MacLaren R E
Oxford Eye Hospital and Nuffield Laboratory of Ophthalmology, University of Oxford.
Ophthalmologe. 2012 Feb;109(2):121-8. doi: 10.1007/s00347-011-2453-3.
Genetic mutations are the cause of inherited retinal dystrophies. The underlying genetic basis of these diseases suggests that a gene therapy approach is logical either to replace or reduce the expression of defective genes. The first proof-of-concept clinical studies in patients with Leber's congenital amaurosis have suggested that retinal gene therapy is safe and potentially effective, at least for specific disease entities. In contrast to pharmacological treatment gene therapy has the advantage of being able to express a protein within specific cell populations and is a potentially definitive therapy. Besides replacing deficient genes in inherited diseases, additional strategies that might broaden the application of retinal gene therapy are also being developed. These include the permanent expression of neuroprotective substances or photosensitive molecules (so-called optogenetics). This overview discusses the current clinical strategies and potential problems of retinal gene therapy.
基因突变是遗传性视网膜营养不良的病因。这些疾病的潜在遗传基础表明，基因治疗方法在逻辑上可以用于替代或减少缺陷基因的表达。针对莱伯先天性黑蒙患者的首批概念验证临床研究表明，视网膜基因治疗是安全且可能有效的，至少对于特定疾病实体是如此。与药物治疗相比，基因治疗具有能够在特定细胞群体中表达蛋白质的优势，并且是一种潜在的确定性治疗方法。除了在遗传性疾病中替代缺陷基因外，还在开发可能拓宽视网膜基因治疗应用范围的其他策略。这些策略包括神经保护物质或光敏分子的永久表达（所谓的光遗传学）。本综述讨论了视网膜基因治疗的当前临床策略和潜在问题。
