IMMUNOPATHOLOGY IN EYES WITH EXPERIMENTAL AND CLINICAL OCULAR DISEASES

实验性和临床眼部疾病的眼部免疫病理学

• 批准号: 6106829
• 负责人: Chi-Chao 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/6106829
• 关键词: MHC class II antigen; autoimmune disorder; cytokine; disease /disorder model; eye disorder; eyelid disorder; human tissue; immunocytochemistry; immunoglobulin genes; immunopathology; in situ hybridization; inflammation; laboratory mouse; leukocyte activation /transformation; lymphoma; macrophage; neutrophil; nitric oxide; polymerase chain reaction; retina disorder; transforming growth factors; uveitis

The identity and topographic localization of immunocompetent cells and the alteration of cellular markers on ocular resident cells in animals with various experimental uveitis were analyzed by immunohistochemistry, in situ hybridization, and polymerase chain reaction (PCR). Previously, we have demonstrated that T lymphocytes are the predominant infiltrating cells in experimental autoimmune uveoretinitis and experimental melanin-induced uveitis, both macrophages and polymorphonuclear neutrophils are the predominant infiltrating cells in endotoxin-induced uveitis, while all types of leukocytes are present in murine experimental blepharitis. Cytokines and inflammatory mediators play an important role in the immunopathogenesis of ocular inflammation. Expressions of major histocompatibility class (MHC) II antigens, adhesion molecules and apoptotic markers are observed on ocular resident cells during the inflammatory process. In FY1998 we have identified the kinetics of Th1 and Th2 cytokines, Fas, FasL, bcl-2 and Bax in the eyes of both animal models and human specimens with uveitis. Using microdissection and PCR, we have identified rearrangement of the immunoglobulin heavy chain gene and bcl-2 translocation in primary intraocular lymphoma cells. These lymphoma cells also produce IL-10 mRNA and IL-10 in the vitreous which can aid diagnosis. We have demonstrated the foamy "stromal" cells in the retinal angioma of von Hippel-Lindau (VHL) disease have loss of the VHL gene, a tumor suppressor gene. In consequence it decreases normal VHL protein translation that interferes with elongin and induce vascular endothelium growth factor to promote neovascularization. The combination of microdissection and molecular techniques helps us to study the selective minute population of cells and their genetics. Elucidating the immunopathological role of the relationship between the infiltrating cells and ocular resident cells will aid in better understanding and management of various ocular diseases in patients.

身份和地形定位 免疫活性细胞和细胞标志物的改变 患有各种实验性葡萄膜炎的动物的眼部常驻细胞 通过免疫组织化学、原位杂交等方法进行分析 聚合酶链反应（PCR）。此前，我们有 证明 T 淋巴细胞是主要的浸润细胞 实验性自身免疫性葡萄膜视网膜炎中的细胞和实验性 黑色素诱发的葡萄膜炎，巨噬细胞和多形核细胞 中性粒细胞是主要的浸润细胞 内毒素引起的葡萄膜炎，同时存在所有类型的白细胞 在小鼠实验性睑缘炎中。细胞因子和炎症 介质在免疫发病机制中发挥重要作用 眼部炎症。主要组织相容性类别的表达 (MHC) II 抗原、粘附分子和凋亡标记物 在炎症过程中观察到眼部驻留细胞。 在 1998 财年，我们确定了 Th1 和 Th2 的动力学 两只动物眼中的细胞因子、Fas、FasL、bcl-2 和 Bax 患有葡萄膜炎的模型和人体标本。使用显微解剖 和 PCR，我们发现了免疫球蛋白的重排 原发性眼内重链基因和bcl-2易位 淋巴瘤细胞。这些淋巴瘤细胞还产生 IL-10 mRNA 玻璃体中的 IL-10 可以帮助诊断。我们有 证明了视网膜血管瘤中的泡沫状“基质”细胞 von Hippel-Lindau (VHL) 病具有 VHL 基因缺失， 肿瘤抑制基因。结果它会降低正常的 VHL 干扰延长素并诱导血管生成的蛋白质翻译 内皮生长因子促进新生血管形成。这 显微切割和分子技术的结合帮助我们 研究选择性微小细胞群及其遗传学。 阐明这种关系的免疫病理学作用 浸润细胞和眼部驻留细胞之间的相互作用将有助于 更好地了解和治疗各种眼部疾病 患者。