Stieger Knut, Lhériteau Elsa, Moullier Phillip, Rolling Fabienne
Laboratoire de Thérapie Génique, INSERM U649, CHU Hôtel-Dieu, Bâtiment J. Monnet, 30 Avenue J. Monnet, 44035 Nantes cedex 01, France. [corrected]
ILAR J. 2009;50(2):206-24. doi: 10.1093/ilar.50.2.206.
Retinal gene therapy holds great promise for the treatment of inherited and noninherited blinding diseases such as retinitis pigmentosa and age-related macular degeneration. The most widely used vectors for ocular gene delivery are based on adeno-associated virus (AAV) because they elicit minimal immune responses and mediated long-term transgene expression in a variety of retinal cell types. Extensive preclinical evaluation of new strategies in large animal models is key to the development of successful gene-based therapies for the retina. Because of differences in the retinal structures among species and unique structures such as the macula and fovea in the primate retina, nonhuman primates are widely used as preclinical animal models. But the observation of inherited retinal degenerations in dogs, which share a number of clinical and pathologic similarities with humans, has led to the characterization of several canine models for retinal diseases, one of which has already responded successfully to AAV-mediated gene therapy. This article presents a review and detailed discussion of the various large animal models available for the study of AAV-mediated gene-based therapies in the retina.
视网膜基因治疗在治疗诸如色素性视网膜炎和年龄相关性黄斑变性等遗传性和非遗传性致盲疾病方面具有巨大潜力。用于眼部基因递送的最广泛使用的载体基于腺相关病毒（AAV），因为它们引发的免疫反应最小，并能在多种视网膜细胞类型中介导长期转基因表达。在大型动物模型中对新策略进行广泛的临床前评估是开发成功的视网膜基因疗法的关键。由于物种间视网膜结构的差异以及灵长类视网膜中诸如黄斑和中央凹等独特结构，非人灵长类动物被广泛用作临床前动物模型。但是对狗的遗传性视网膜变性的观察发现，狗在临床和病理方面与人类有许多相似之处，这导致了几种视网膜疾病犬模型的特征描述，其中一种已经成功地对AAV介导的基因治疗做出了反应。本文对可用于研究视网膜中AAV介导的基因疗法的各种大型动物模型进行了综述和详细讨论。
