视网膜色素变性（retinitis pigmentosa，RP）是一组以感光细胞功能异常和渐进性死亡为特征的遗传性视网膜疾病，目前已有100多个RP相关的致病基因被报道，但这些基因突变导致RP的分子机制尚不完全清楚，临床上也无有效的针对性治疗方法。建立不同RP基因缺陷的动物模型是揭示视网膜色素变性发病机制并发展有效的治疗手段的关键。前期工作中我们建立了成熟的斑马鱼RP基因敲除和视网膜变性研究方法。本项目拟在此基础上应用TALEN技术构建含15种基因敲除的RP斑马鱼品系，应用ERG、HE染色、免疫荧光、电镜以及蛋白组学等技术对其表型进行系统地鉴定，阐明不同基因突变引起RP的分子机制，并在此基础上进行精准治疗尝试。本项目如获资助并成功实施，将拥有世界上含最多RP基因突变的斑马鱼品系，获得较为全面的斑马鱼视网膜变性表型谱，并为揭示RP可能的发病机制及发展RP精准治疗方法奠定基础。

Retinitis pigmentosa (RP) is a group of inherited retinal degeneration diseases, caused by gradual dysfunction and death of photoreceptor cells. So far, at least 100 RP causative genes have been identified, but the molecular mechanism of how these gene mutations cause RP is still not fully understood, and also there is no targeted treatment. It is essential to establish good animal models to explore the possibility of studying the pathogenesis of RP and performing precision treatment. In the previously studies, our have developed effective methods to knockout targeted genes in zebrafish, and techniques for investigate for retinitis pigmentosa. Here we are aimed to generate 15 RP disease-causing gene knockout zebrafish strains by using TALEN technology and systematically analyze their retinal phenotypes. Further using the gene knockout zebrafish manifesting retinal degeneration, we intent to screen the collectively changed pathways shared by different knockout zebrafish and the exclusively changed pathways caused by certain gene’s ablation by performing proteomics study, and try to find effective precision treatment methods based on these results. Our work may establish the biggest zebrafish research platform for retinitis pigmentosa at present, obtain the comprehensive phenotypic spectrum of retinal degeneration zebrafish, reveal the probable pathogenesis of RP, and open a new avenue for developing therapic methods for Retina degeneration in the future.