IMMUNOLOGIC MECHANISMS OF OCULAR DISEASE

本项目的标题已从“细胞粘附分子在 从“眼部炎症”到“眼部疾病的免疫机制”， 扩大实验范围，包括细胞粘附的作用 分子和其他免疫因子，包括细胞因子， 眼部疾病，特别是葡萄膜炎、眼部恶性肿瘤， 与艾滋病有关的眼病。 此外，该项目此前在 在免疫学实验室中列出，但现在在临床 分支。 本项目的目的是研究免疫学机制 参与眼部炎症和眼部恶性肿瘤的发病机制 并根据这些数据开发和测试治疗方法。 最近我们 集中在细胞粘附分子和细胞因子在 眼部炎症性疾病的发展。 细胞粘附分子 是抗原致敏和迁移的重要表面蛋白 白细胞转移到炎症部位。 我们目前正在调查 作为葡萄膜炎和其它眼炎的治疗的阻断CAM的化合物 炎症性疾病。 在过去的一年里，我们发现， 注射抗CAMs的单克隆抗体，淋巴细胞功能- 相关抗原-1（LFA-1）和Mac-1，可以抑制 葡萄膜炎超过66%。 相反，用单克隆抗体治疗 抗第三种CAM--血管粘附分子-1（VCAM-1）的抗体失败 以抑制体内疾病。 抗这些细胞粘附分子的抗体 也能抑制体外淋巴细胞增殖达70%。 我们还研究了白细胞介素-12在急性胰腺炎发生发展中的作用。 眼内炎症，并显示全身给予抗体 针对IL-12的抑制加重了内毒素诱导的葡萄膜炎。 同样地， 眼内IL-12抑制疾病。 这些数据表明内毒素- 诱导的葡萄膜炎可能是TH 2依赖性疾病。 最后，我们调查了 许多治疗剂在眼损伤动物模型中的作用 炎症 我们证明了MDL 28，842，一种S-腺苷酸抑制剂， L-同型半胱氨酸水解酶，减少眼部炎症的动物， 实验性自身免疫性葡萄膜炎（EAU）。 在其他实验中，我们发现 局部使用肝素可以抑制过敏性 由肥大细胞脱颗粒引起的结膜炎。

The title of this project has been changed from "cell adhesion molecules in ocular inflammation" to "immunologic mechanisms of ocular disease" to refle the broadening scope of experiments to encompass the role of cell adhesion molecules and other immunologic factors, including cytokines, in the pathogenesis of ocular diseases, particularly uveitis, ocular malignancy, a ocular disease related to AIDS. In addition, this project was previously listed in the Laboratory of Immunology but is now listed in the Clinical Branch. The goal of this project is to study the immunologic mechanisms involved in the pathogenesis of ocular inflammation and ocular malignancy and to develop and test therapies based on these data. Recently, we have concentrated on the role of cell adhesion molecules and cytokines in the development of ocular inflammatory disease. Cell adhesion molecules (CAMs) are surface proteins important for antigen sensitization and the migration of leukocytes to sites of inflammation. We are currently investigating compounds that block CAMs as a treatment for uveitis and other ocular inflammatory diseases. During the past year, we showed that a single injection with a monoclonal antibody against the CAMs, lymphocyte function- associated antigen-1 (LFA-1) and Mac-1, can inhibit the development of uveitis by more than 66 percent. In contrast, treatment with a monoclonal antibody against a third CAM, vascular adhesion molecule-1 (VCAM-1) failed to inhibit in vivo disease. Antibodies against these cell adhesion molecul also inhibited lymphocyte proliferation in vitro by up to 70 percent. We also studied the role of interleukin-12 on the development of acute intraocular inflammation and showed that systemically administered antibody against IL-12 exacerbates the endotoxin-induced uveitis. Similarly, intraocular IL-12 inhibited disease. These data suggest that endotoxin- induced uveitis may be a TH2-dependent disease. Finally, we investigated the effect of a number of therapeutic agents in animal models of ocular inflammation. We demonstrated that MDL 28,842, an inhibitor of S-adenosyl- L-homocysteine hydrolase, decreases the ocular inflammation in animals with experimental autoimmune uveitis (EAU). In other experiments, we showed that topically administered heparin inhibits the development of allergic conjunctivitis induced by mast cell degranulation.