人视网膜类器官睫状缘区干细胞在视网膜损伤修复中的作用研究

睫状缘区视网膜干细胞（RSCs）具有特定的可直接分化为视网膜细胞的潜能，其移植有望成为治疗视网膜变性疾病的最有效方式。但功能完备的RSCs数量稀少且难以获取，极大地限制了其基础及临床应用研究。视网膜类器官可高度模拟体内视网膜发育过程，我们前期研究发现，人视网膜类器官中存在充足且易获取的睫状缘区RSCs，其能够显著改善视网膜成活率和存活状态，且视网膜切除后的睫状缘区仍可再生视网膜，但这类睫状缘区RSCs是否具有再生修复视网膜的潜能尚不清楚。本项目拟在前期工作的基础上，基于人视网膜类器官，鉴定睫状缘区RSCs的生物学特性、分子特征及表面标志物；揭示其在体外视网膜损伤修复中的作用，并绘制单细胞转录图谱解析视网膜再生修复过程；最后探索睫状缘区RSCs移植治疗视网膜色素变性小鼠的效果。本项目旨在揭示人视网膜类器官睫状缘区RSCs再生修复视网膜的潜能，为应用RSCs治疗视网膜变性疾病奠定关键科学基础。

Retinal stem cells (RSCs) in the ciliary marginal zone (CMZ) have specific potential to differentiate directly into retinal cells. Their transplantation is expected to be the most effective way for the treatment of retinal degeneration. However, the scarce number of fully functional RSCs and difficulty in their obtaining greatly limit related basic research as well as clinical application. The development process of retina in vivo could be highly mimicked by retinal organoids. Our previous study showed that there are sufficient and easily accessible CMZ-RSCs of human retinal organoids, which significantly improve the survival rate and status of neural retina. What’s more, retina can be regenerated by the CMZ. However, whether such CMZ-RSCs of human retinal organoids have the ability to regenerate and repair retina remains so far, still unclear. Therefore, using human retinal organoid as model, this project intends to identify the biological characteristics, molecular properties and surface markers of CMZ-RSCs to further clarify their role in the repair of retinal injury in vitro；Meanwhile, a single-cell transcriptomic atlas will be obtained to reveal the process of retinal regeneration and repair. Finally, the efficacy of transplantation of CMZ-RSCs on the treatment of retinitis pigmentosa mice will be explored. The knowledge generated in this project will help to reveal the potential of CMZ-RSCs of human retinal organoids for retinal regeneration and repair, and to lay a key scientific foundation for the application of RSCs in the treatment of retinal degeneration.