我国有300万角膜盲人需行角膜移植复明，术后免疫排斥是失败的最重要原因。经典的“角膜缘免疫排斥途径”理论难以解释临床常见的内皮型排斥现象，且防治效果不佳。我们研究发现：角膜移植排斥发生时，眼内虹膜-睫状体-房水中出现大量免疫细胞，眼前房植入免疫抑制缓释药物能有效防治排斥反应。由此提出，“虹膜-睫状体-房水途径”可能是造成角膜移植免疫排斥的另一重要通路，但供体角膜内皮细胞抗原在该通路中如何被识别并启动免疫排斥发生的机理仍不清楚。因此，本课题拟对眼前房中抗原递呈细胞识别异体角膜内皮抗原、启动免疫排斥反应的信号机制，以及眼前房免疫微环境变化对虹膜-睫状体中Treg细胞c-Rel/mTOR活性和免疫抑制功能的影响进行研究，旨在阐明“虹膜-睫状体-房水途径”在角膜移植免疫排斥过程中的作用及其机理，并进一步揭示眼前房植入免疫抑制缓释药物防治角膜移植排斥的靶点，指导新剂型的研发和应用。

There are above 3 million blind people waiting for corneal transplantation to recover the sight. However, postoperative rejection is still the most important reason that causes the failure of transplantation. Classical theory cannot explain the corneal endothelium-type rejection, and conventional clinical anti-rejection therapy seems ineffective to prolong donor corneal survival periods. Our study has found that the iris-ciliary body-aqueous humor shows numerous immune cell infiltration during corneal graft rejection. Moreover, the implantation of immunosuppressive drug-delivery system in the anterior chamber seems to be more effective than conventional treatments to control the corneal transplantation rejection. These findings suggest that the intraocular “iris-ciliary body-aqueous humor" may represent another important pathway that mediates immune rejection of corneal transplantation. However, the corneal endothelial antigen recognition and the initiating mechanism of immune rejection in the intraocular pathway remained unclear. Therefore, in the present study, we will explore the mechanisms of corneal endothelial antigen recognition and immune rejection initiation, the influence of anterior chamber microenvironment change on the c-Rel/mTOR activity and function of Treg cells. The aim of this project is to clarify the function of "iris-ciliary body-aqueous humor" pathway in the rejection reaction of corneal transplantation, and the targets of anterior chamber-implanted sustained releasing immunosuppressive drugs for preventing the corneal graft rejection. The results will be helpful for the development and clinical application of new drug forms for the prevention of corneal transplantation rejection.