IMMUNOBIOLOGY OF CORNEAL ALLOGRAFTS

同种异体角膜移植物的免疫生物学

• 批准号: 2459106
• 负责人: JERRY NIEDERKORN
• 金额: $ 22.26万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2459106
• 关键词: MHC class II antigen; angiogenesis; cell adhesion molecules; cornea; cytotoxic T lymphocyte; delayed hypersensitivity; homologous transplantation; hyperbaric oxygen therapy; immune tolerance /unresponsiveness; keratoplasty; laboratory mouse; monoclonal antibody; radiation immunosuppression; tissue /cell culture; transplant rejection; ultraviolet radiation

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.

角膜移植是最古老的，可以说是最成功的 器官移植的形式。 仅在美国， 每年进行40,000次角膜移植。 尽管很高 角膜造成术的成功率，大约10％的角膜移植物 由于免疫拒绝，将失败。 因此，开发新的和 防止免疫拒绝的更有效的策略 角膜同种异体移植物可能会对保存产生巨大影响 恢复大量个人的视力。 远程目标 本研究项目的开发，评估和表征 防止诱导角膜移植排斥的新型策略 并降低长期宿主的晚期移植拒绝的风险 术语清除角膜移植物。 该项目的直接特定目标 为：（l）利用紫外线B辐照（UVB）呈现角膜 移植物非免疫原性和可能的​​耐受性； （2）利用 针对细胞粘附分子的抗体作为一种方法 防止免疫效应细胞功能和诱导 免疫耐受性； （3）使用高压O2治疗作为一种方法 用于降低角膜移植物的免疫原性； （4）确定 诱导II类MHC抗原表达对生存的影响 以前清除角膜移植物； （5）评估免疫原性 顺序角膜同种异体移植物（即，“无声刺激” 延迟类型的超敏反应）； （6）确定 角膜同种异体移植生存的自发角膜新血管化。这 这些调查中的大多数将使用鼠标模型来解决 穿透性角膜生成形术。 这些调查的结果应该 提供有关角膜免疫生物学的重要见解 同种异体移植以及特定免疫学策略的可行性 促进角膜同种异体移植生存。