The relationship between the neurosensory photoreceptors and the adjacent retinal pigment epithelium (RPE) controls not only normal retinal function, but also the pathogenesis of hereditary retinal degenerations. The molecular bases for both primary photoreceptor and RPE diseases that cause blindness have been identified. Gene therapy has been used successfully to slow degeneration in rodent models of primary photoreceptor diseases, but efficacy of gene therapy directed at photoreceptors and RPE in a large-animal model of human disease has not been reported. Here we study one of the most clinically severe retinal degenerations, Leber congenital amaurosis (LCA). LCA causes near total blindness in infancy and can result from mutations in RPE65 (LCA, type II; MIM 180069 and 204100). A naturally occurring animal model, the RPE65-/- dog, suffers from early and severe visual impairment similar to that seen in human LCA. We used a recombinant adeno-associated virus (AAV) carrying wild-type RPE65 (AAV-RPE65) to test the efficacy of gene therapy in this model. Our results indicate that visual function was restored in this large animal model of childhood blindness.

中文翻译：

---

基因治疗可以在儿童失明的犬模型中恢复视力。

神经感觉光感受器和邻近的视网膜色素上皮（RPE）之间的关系不仅控制正常的视网膜功能，而且控制遗传性视网膜变性的发病机理。已经确定了引起失明的原发性光感受器和RPE疾病的分子基础。基因疗法已成功用于减缓啮齿类动物原发性光感受器疾病的退化，但是针对人类疾病的大动物模型中针对光感受器和RPE的基因治疗的功效尚未见报道。在这里，我们研究了最临床上最严重的视网膜变性之一，莱伯先天性黑蒙（LCA）。LCA导致婴儿期几乎完全失明，并且可能由RPE65（LCA，II型； MIM 180069和204100）中的突变引起。RPE65-/-狗是天然动物模型，患有早期和严重的视觉障碍，与人类LCA相似。我们使用携带野生型RPE65（AAV-RPE65）的重组腺相关病毒（AAV）来测试该模型中基因治疗的功效。我们的结果表明，在儿童失明的这种大型动物模型中，视觉功能得以恢复。