IMMUNOPATHOLOGY IN EYES WITH EXPERIMENTAL AND CLINICAL OCULAR DISEASES

实验性和临床眼部疾病的眼睛免疫病理学

• 批准号: 3755558
• 负责人: C-C CHAN
• 金额: --
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3755558
• 关键词: Rodentias; T lymphocyte; autoimmune disorder; cellular immunity; conjunctivitis; disease /disorder model; electron microscopy; human tissue; immunocytochemistry; immunopathology; in situ hybridization; inflammation; leukocyte activation /transformation; retina disorder; retinal pigment epithelium; toxoplasmosis; uveitis; vascular endothelium

The identity and topographic localization of immunocompetent cells and the alteration of surface markers on ocular resident cells in animals with vari s experimental uveitis were analyzed by immunohistochemical studies and in situ hybridization. Previously, we have demonstrated that T lymphocytes were the predominantly infiltrating cells in experimental autoimmune uveoretinitis (EAU), yet both macrophages and polymorphonuclear neutrophils were the predominantly infiltrating cells in endotoxin-induced uveitis (EIU). Cytokines (e.g., gamma-interferon), inflammatory mediators (e.g., nitric oxide), and some retinal proteins (e.g., S-antigen (S-Ag)) pl an important role in the immunopathogenesis of EAU and EIU. Agents that modulate them can alter the immunopathology of the experimental model. For example, prolonged corticosteroid therapies enhance S-Ag expression in nonretinal ocular tissues of rats with EAU. Several new animal models, including experimental melanin-protein-induced uveitis (EMIU), experimental blepharitis, murine allergic conjunctivitis, a murine toxoplasmosis, have been developed and studied. They represented different entities of uveitis in humans. EMIU closely resembles Vogt- Kayanagi-Harada syndrome and sympathetic ophthalmia; experimental blepharitis induced by immunization of monoclonal antibody of Id16/6 resembles idiopathic blepharitis; murine allergic conjunctivitis induced by compound 48/80 resembles allergic conjunctivitis; murine toxoplasmosis infected with T. gondii resembles acquired ocular toxoplasmosis. Specimens from human ocular tissues with various diseases, including uveitis, retinal and corneal diseases, tumors, and metabolic genetic disorders, are studied using immunohistochemical and in situ hybridization techniques as well as light and electron microscopic examinations. In uveitis, immunocompetent cells and lymphokines besides the stimulators (e.g infectious organisms) are valuable adjuncts to the clinical diagnosis and t understanding of pathogenesis of the diseases. In nonuveitic conditions, alteration of cellular membrane surface markers and intracytoplasmic organelles of the ocular resident cells (e.g., crystalline inclusions in Be ti's crystalline dystrophy; B-cell marker in intraocular lymphoma) may reflect cellular damage and abnormalities in these diseases. Elucidating the immunopathological role of the relationships between infiltrating inflammat y or malignant cells and other resident cells in the clinical behavior of various diseases will increase our understanding of human ocular disorders and provide better treatment.

免疫活性细胞的身份和拓扑定位以及免疫活性细胞的功能。 不同类型视网膜瓦里动物眼常驻细胞表面标志物的改变 S 实验性葡萄膜炎的免疫组化研究和分析， 原位杂交 以前，我们已经证明，T淋巴细胞 是实验性自身免疫性疾病中主要的浸润细胞 葡萄膜视网膜炎（EAU），但巨噬细胞和多形性 中性粒细胞是内毒素诱导的主要浸润细胞。 葡萄膜炎（EIU）。 细胞因子（例如，γ-干扰素），炎症介质 (e.g.,一氧化氮），和一些视网膜蛋白（例如，S-抗原（S-Ag） 在EAU和EIU的免疫发病机制中起重要作用。 的试剂 调节它们可以改变实验模型的免疫病理学。 为 例如，长期的皮质类固醇治疗可增强S-Ag表达， EAU大鼠的非视网膜眼组织。 几种新的动物模型，包括实验性黑色素蛋白诱导的 葡萄膜炎（EMIU），实验性睑缘炎，小鼠过敏性结膜炎，a 鼠弓形虫病，已经开发和研究。 他们代表 不同类型的葡萄膜炎。 EMIU很像沃格特- Kayanagi-Harada综合征和交感性眼炎;实验性 Id 16/6单克隆抗体免疫诱导的睑缘炎 类似于特发性睑缘炎; 化合物48/80类似于过敏性结膜炎;鼠弓形虫病 感染T.刚地类似于获得性眼弓形体病。 来自患有各种疾病的人眼组织的标本，包括 葡萄膜炎、视网膜和角膜疾病、肿瘤和代谢遗传 使用免疫组织化学和原位杂交技术研究 技术以及光学和电子显微镜检查。 在 葡萄膜炎、免疫活性细胞和淋巴因子 感染性微生物）对临床诊断和试验 了解疾病的发病机制。 在无色素膜的情况下， 细胞膜表面标记物和胞浆内标记物的改变 眼常驻细胞的细胞器（例如，Be中的结晶包裹体 ti的 晶体营养不良;眼内淋巴瘤中的B细胞标志物）可能反映 这些疾病中的细胞损伤和异常。 阐明 浸润性炎症与免疫病理学的关系 y 或恶性细胞和其他常驻细胞的临床行为， 各种疾病将增加我们对人类眼部疾病的了解 并提供更好的治疗。