IMMUNOBIOLOGY OF CORNEAL ALLOGRAFTS

角膜移植是最古老的，也是最成功的。 器官移植的形式。仅在美国，就结束了 每年进行40,000例角膜移植。尽管情绪高涨 角膜移植成功率，约占角膜移植物的10% 会因为免疫排斥反应而失败。因此，开发新的和 预防免疫排斥反应的更有效策略 同种异体角膜移植可能会对保存和 在大量个体中恢复视力。远距离目标 本研究项目的目的是开发、评估和表征 预防角膜移植排斥反应诱导的新策略 并降低长期移植排斥反应的风险 术语透明角膜移植。该项目的直接具体目标 ：(L)利用紫外线B照射(UVB)渲染角膜 移植物非免疫原性和可能的耐受性；(2)利用 抗细胞黏附分子抗体作为一种治疗 预防免疫效应细胞功能和诱导 免疫耐受；(3)高压氧治疗作为一种方法 以降低角膜移植物的免疫原性；(4)测定 诱导表达第II类MHC抗原对人肝癌细胞存活的影响 早期透明角膜移植；(5)评价免疫原性 连续的同种异体角膜移植(即 迟发性超敏反应)；以及(6)确定 自发性角膜新生血管对同种异体角膜移植存活的影响。这个 这些研究中的大多数将使用小鼠模型进行研究。 穿透性角膜移植。这些调查的结果应该是 提供对角膜免疫生物学的重要见解 同种异体移植和特定免疫学策略的可行性 促进同种异体角膜移植存活。

Corneal transplantation is the oldest and arguably, the most successful form of organ transplantation. In the United States alone, over 40,000 corneal transplants are performed annually. In spite of the high success rate of keratoplasty, approximately 10% of the corneal grafts will fail due to immunological rejection. Thus, developing new and more effective strategies for preventing immunological rejection of corneal allografts could have an enormous impact on the preservation and restoration of vision in large number of individuals. The long range goal of the present research project is to develop, evaluate, and characterize novel strategies for preventing the induction of corneal graft rejection and for reducing the risk of late graft rejection in hosts bearing long term clear corneal grafts. The immediate specific aims of this project are: (l) utilization of ultraviolet B irradiation (UVB) to render corneal grafts nonimmunogenic and possibly tolerogenic; (2) utilization of antibodies against cell adhesion molecules as a method for preventing immunological effector cell function and for inducing immunological tolerance; (3) use of hyperbaric O2 treatment as a method for reducing the immunogenicity of corneal grafts; (4) determine the effect of induced class II MHC antigen expression on the survival of previously clear corneal grafts; (5) evaluate the immunogenic potential of sequential corneal allografts (i.e., "silent stimulation" of delayed type hypersensitivity); and (6) to determine the specific role of spontaneous corneal neovascularization on corneal allograft survival. The majority of these investigations will be addressed using a mouse model of penetrating keratoplasty. The results from these investigations should provide important insights into the immunobiology of corneal allografts and the feasibility of specific immunological strategies for promoting corneal allograft survival.