Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy.

摘要: Leber congenital amaurosis (LCA) is a rare hereditary retinal degeneration caused by mutations in more than dozen genes. RPE65, one of these mutated genes, highly expressed the pigment epithelium where it encodes retinoid isomerase enzyme essential for production chromophore which forms visual rod and cone photoreceptors retina. Congenital loss due to RPE65-deficiency together with progressive photoreceptor cause severe vision. RPE65-associated LCA recently gained recognition outside specialty ophthalmic circles early success achieved three clinical trials gene therapy using recombinant adeno-associated virus (AAV) vectors. The were built on multitude basic, pre-clinical research defining pathophysiology disease human subjects animal models, demonstrating proof-of-concept (augmentation) therapy. Substantial gains function trial participants provided evidence physiologically relevant biological activity resulting from newly introduced gene. This article reviews current knowledge dysfunction models patients RPE65 disease, examines consequences terms improvement vision reported.