角膜盲是我国第二位致盲性眼病，角膜移植是复明的唯一手段，但术后的免疫排斥反应是移植失败的最主要原因。课题组前期研究发现，发生免疫排斥小鼠模型角膜植片存在免疫细胞自噬异常现象，而雷帕霉素（自噬激动剂）能有效防治角膜移植免疫排斥反应的发生。雷帕霉素体内特异性结合物mTOR是自噬上游通路最主要的细胞因子靶点。以上结果提示免疫细胞mTOR-自噬通路在免疫排斥过程中发挥重要的作用，但具体机制不明。基于此，研究团队拟：1）通过对临床因排斥导致移植失败的样本和发生免疫排斥小鼠角膜移植模型进行研究，明确角膜移植术后免疫排斥反应过程中自噬异常的免疫细胞类型；2）利用小鼠角膜移植模型研究mTOR-自噬通路在免疫排斥反应过程中的作用；3）通过体外实验明确mTOR-自噬通路参与角膜移植免疫排斥的病理机制。通过本研究可初步明确mTOR-自噬通路在角膜移植免疫排斥中的作用，为临床防治角膜移植免疫排斥反应提供理论基础。

Corneal blindness is the second major ocular disease causing blind in China, and corneal transplantation is the only way for vision recovery. However, the postoperative immune rejection is the main reason of graft failure. Our previous studies have found that there is abnormal autophagy of immune cells in the failed graft of mice model with immune rejection. And rapamycin (autophagy agonist) can effectively prevent the immune rejection. mTOR, the specific conjugate of rapamycin in vivo, is the main cytokine target in autophagy upstream pathways. The previous results suggest that immune cells mTOR-autophagy signaling pathway has played an important role in immune rejection, but the specific mechanism is still not clear. Based on this, the group plans: 1) research on samples with clinical failed graft caused by immune rejection and mice models, so as to clarify the types of immune cells with abnormal autophagy during immune rejection after cornea transplantation; 2) explore the role of mTOR-autophagy pathway in immune rejection with corneal transplantation models in mice; 3) explore the pathogenesis of mTOR-autophagy signaling pathway in immune rejection after corneal transplantation via in vitro experiments. Through this study, the role of mTOR-autophagy signaling pathway in immune rejection after corneal transplantation can be preliminarily clarified, to provide theoretical basis for clinical prevention and treatment of immune rejection after corneal transplantation.