视网膜变性疾病是一类以感光细胞变性死亡导致失明的不可逆致盲眼病。视网膜移植被认为是最具前景的治疗手段。最近，少数研究组包括我们用人诱导多能干细胞hiPSC培育出了三维立体视网膜组织（3D视网膜），此技术突破为该类疾病的视网膜移植复明治疗带来了希望。然而，hiPSC来源3D 视网膜临床应用的安全性和有效性问题有待阐明。本项目围绕hiPSC来源视网膜的临床转化关键问题进行系统研究，采用无病毒，无饲养层及Xeno-free系统构建、培养视网膜变性患者特异的hiPSC，并诱导分化为3D 视网膜组织，期望开发临床应用级别的3D视网膜培养系统, 为临床提供充足、安全的视网膜供体；构建光感受器损伤兔动物模型，进行3D视网膜片的移植实验，评价眼内移植片的安全性和有效性，为 hiPSC 来源3D视网膜移植治疗视网膜变性疾病提供依据，促进视网膜移植治疗及个体化医学治疗的开展，造福失明患者，意义重大。

Retinal degenerative disorder is a group of diseases involving the gradual loss or dysfunction of photoreceptors, causing irreversible blindness. Retinal transplantation replacing the lost cells has been believed to be the most promising therapies. Recently, a few of groups including us have developed technology to generate 3D retinas from hiPSC, which provide a highly convenient donor tissue source for the treatment of these diseases through retinal transplantation. However, the therapeutic efficacy and safety of hiPSC-derived 3D retina are unclear now. This proposal aims to address these key issues with advanced technologies through following approaches: 1) develop viral-free, feeder-free and xeno-free technology to establish and culture patient specific hiPSC, and induce them into 3D retinas with the aim to establish a novel clinical-grade hiPSC-derived 3D retina culture system; 2) establish an animal model with retinal degeneration, and transplant hiPSC-derived 3D retinas into its subretinal space. We hope that data and results acquired from this study could clarify the above efficacy and safety issues related to clinical application for the treatment of retinal degenerative diseases, promote the clinical translation research and personal medicine of hiPSC-derived 3D retina and finally treat the diseases.