DIAGNOSIS AND TREATMENT OF OCULAR INFLAMMATORY DISEASE

该项目的目标是开发改进的方法， 诊断和治疗眼部炎性疾病，包括 葡萄膜炎，眼恶性肿瘤， 和眼部过敏。 眼部炎症的发展取决于 特异性炎性细胞因子和细胞粘附的表达 导致白细胞归巢和迁移到 the eye. 使用我们开发的眼部过敏的小鼠模型， 实验室，我们证明了过敏性结膜炎的恶化， γ-干扰素基因敲除小鼠对眼变态反应的抗性 白细胞介素-4基因敲除小鼠提示重要的免疫调节 这两种细胞因子的功能。在过去的一年里，我们还展示了 通过阻断两种细胞， 粘附分子、抗（ICAM-1）的单克隆抗体或其 淋巴细胞功能相关分子-1（LFA-1）配体抑制 过敏性结膜炎的发展。 我们先前已经表明 阻断细胞粘附分子可以抑制其他形式的眼部炎症， 炎症如葡萄膜炎。 治疗眼部疾病的临床试验 计划通过阻断细胞粘附分子来引起炎症。 临床研究集中在诊断和治疗 葡萄膜炎和眼内淋巴瘤。 原发性中枢神经系统的诊断 神经系统淋巴瘤（PCNSL）通常通过鉴定 大脑、脑脊液（CSF）中的恶性淋巴细胞，或 玻璃体;然而，这些细胞很少，易碎，误诊 即使在适当制备的样品中也可能发生。我们发现， 眼内PCNSL的发生与 IL-10相对于IL-6的玻璃体水平以及 这些细胞因子可用于诊断这种恶性肿瘤。 正在进行的临床试验正在研究视觉的自然史 和视觉功能的影响。 NEI还 一直在研究口服 抗原作为葡萄膜炎的治疗。 II型胶原蛋白可能是 类风湿性关节炎患者的自身免疫抗原 关节炎 我们正在进行I/II期开放标签试验， II型胶原蛋白对幼年型类风湿关节炎患者的治疗作用 关节和眼睛疾病。

The goal of this project is to develop improved methods for diagnosing and treating ocular inflammatory disease and encompasses both laboratory and clinical studies of uveitis, ocular malignancy, and ocular allergy. The development of ocular inflammation depends on the production of specific inflammatory cytokines and the expression of cell adhesion molecules that lead to the homing and migration of leukocytes into the eye. Using a murine model of ocular allergy developed in our lab, we demonstrated an exacerbation of allergic conjunctivitis in gamma-interferon knock out mice and resistance to ocular allergy in interleukin-4 knockout mice suggesting the important immunoregulatory function of these two cytokines. Over the past year we also showed that allergic conjunctivitis could be inhibited by blocking two cell adhesion molecules, a monoclonal antibody against (ICAM-1) or its ligand, lymphocyte function-associated molecule-1 (LFA-1), inhibited the development of allergic conjunctivitis. We have previously shown that blocking cell adhesion molecules inhibits other forms of ocular inflammation such as uveitis. Clinical trials for treating ocular inflammation by blocking cell adhesion molecules are planned. Clinical studies have focused on the diagnosis and treatment of uveitis and intraocular lymphoma. The diagnosis of primary central nervous system lymphoma (PCNSL) is usually made by identifying malignant lymphocytes in the brain, cerebral spinal fluid (CSF), or vitreous; however, these cells are few and friable, and misdiagnosis can occur, even in properly prepared specimens. We showed that the occurrence of PCNSL in the eye was strongly associated with elevated vitreous levels of IL-10 relative to IL-6 and that measurement of these cytokines can be useful for the diagnosis of this malignancy. Ongoing clinical trials are studying the natural history of vision and visual functioning in patients with uveitis. The NEI has also been investigating the safety and efficacy of oral administration of antigens as a treatment for uveitis. Type II collagen is a possible autoimmune antigen in patients with various forms of rheumatoid arthritis. We are conducting a Phase I/II, open label trial of type II collagen for patients with juvenile rheumatoid arthritis with both joint and eye disease.