免疫排斥反应是干细胞治疗年龄相关性黄斑变性(AMD)的最大障碍之一。人类白细胞抗原(HLA）I类分子表达缺失的“通用供体干细胞” (Ucell)具有“免疫豁免权”，但存在成瘤性、功能缺失等安全隐患。我们的前期结果表明这类Ucell诱导分化的视网膜色素上皮细胞(Ucell-RPE)的吞噬功能存在缺陷。本研究拟解析其吞噬缺陷发生的具体阶段和背后的分子机制，结合对缺失HLA I类分子膜表达的小鼠眼组织病理表型的观察，明确HLA I类分子对RPE的重要作用；并通过分析AMD小鼠模型移植了Ucell-RPE后眼组织的病理表型变化，了解其作为移植供体对宿主眼组织的影响，鉴定这类Ucell供体用于治疗AMD是否适用。这项研究将首次阐明HLA I类分子在免疫系统外的吞噬功能并厘清具体机制，揭示HLA I类分子表达缺失的干细胞作为通用移植供体的缺陷，为开发新的通用供体干细胞提供思路，对干细胞治疗有重要意义。

Immune rejection has been the big roadblock for stem-cell based therapy for age-related macular degeneration (AMD). The role of HLA proteins in activating the immune system has led the field of stem cell therapies to develop universal donor stem cell, that eliminated the expression of HLA class I proteins, which is able to reduce the risk of immune rejection of donor tissue but has safety issues, like tumorigenesis. Our results demonstrated that when the surface expression of HLA I protein was eliminated, the phagocytic ability of RPE cells was also impaired. This objectives of this projects are as follows:investigate the functions of HLA I in RPE phagocytosis and the molecule signal pathways behind to identify the importance of HLA I I for RPE; investigate the pathology of eyes in the mice lacking of HLA I to know its in vivo effects on the eyes; Investigate the pathology of the mice eyes transplanted with RPE derived from the defected Ucells or control to know their effects on the degenerated eyes. This study will prove that HLA I plays an important roles in RPE phagocytosis besides its roles in immune response and identify the mechanism behind it; it will also prove the defects of universal donor cells lacking of HLA I as a donor cell for stem-cell based therapy for AMD, which will lead the development of universal donor cells to a new direction and is very meaningful for the development of stem cell therapy.