视网膜常染色体显性遗传病的特点及基因治疗策略

Characteristics of autosomal dominant retinal diseases and gene therapy strategies

遗传性视网膜疾病(IRDs)是主要致盲眼病之一,目前已知有270多个基因突变可以引起此病,最常见的临床类型为视网膜色素变性。IRDs导致的视力障碍当前无法普遍治愈,第1种基因补充疗法在近年来被批准用于治疗常染色体隐性IRDs。由于常染色体显性IRDs致病机制除了少数功能缺失性突变外,通常为功能获得或显性-负性效应,基因补充治疗并非完全有效,并且常染色体显性IRDs临床表现极为复杂,因此目前临床上尚缺乏适当的治疗方法。本文对常染色体显性IRDs的发病机制、临床表现特征以及国际上的治疗方向进行综述,总结引起常染色体显性IRDs的已知常见致病基因,旨在对常染色体显性IRDs有更深入的了解。

Inherited retinal diseases(IRDs),one type of the major eye diseases resulting in blindness,can be caused by more than 270 identified causative genes.The most common form of IRDs is retinitis pigmentosa.There is no generally accepted cure for vision impairment due to IRDs.In recent years,the first gene replacement therapy has been approved for the treatment of autosomal recessive IRDs.Because of the variety of pathogenesis,including gain-of-function and dominant-negative effects in addition to a few loss-of-function mutations,gene replacement therapy of autosomal dominant IRDs is not always effective.The clinical manifestations of autosomal dominant IRDs are extremely complex,and there is no appropriate treatment in clinical practice.The latest progresses in pathogenesis,clinical features,treatment strategies and directions of autosomal dominant IRDs globally were reviewed,and the most common genes causing autosomal dominant IRDs were summarized in this article in order to provide a deeper understanding of autosomal dominant IRDs.