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: 2574498
• 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/2574498
• 关键词: AIDS; B lymphocyte; autoimmune disorder; clinical research; cytokine; disease /disorder model; eye disorder; eye disorder diagnosis; human tissue; immunocytochemistry; immunopathology; in situ hybridization; inflammation; laboratory mouse; leukocyte activation /transformation; lymphoma; nitric oxide; 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 and in situ hybridization. Previously, we have demonstrated that T lymphocytes, in particular the CD4 cells, were the predominant infiltrating cells in experimental autoimmune uveoretinitis (EAU) and experimental melanin-protein induced uveitis (EMIU), yet both macrophages and polymorphonuclear neutrophils were the predominant infiltrating cells in endotoxin-induced uveitis (EIU) and all types of leukocytes were present in murine experimental blepharitis. Cytokines (e.g., lymphokines) and inflammatory mediators (e.g., nitric oxide) play an important role in the immunopathogenesis of uveitis. Expressions of major histocompatibility class (MHC) II antigens and adhesion molecules are observed on ocular resident cells during the inflammatory process. We have studied transforming growth factor-beta (TGF-beta1), one of the cytokines that modulates inflammation in rodent EMIU, murine EIU, and TGF-beta1 transgenic mice. TGF-beta1 inhibits the recurrence of EMIU by shifting Th1 to Th2 cytokine profile. Systemic TGF-beta1 suppresses EIU and serum IL-6 levels. Progressive cataract and transient retinal edema develop in TGF-beta1 transgenic mice. However, no significant differences in the induction of EIU were found between the transgenic mice and the wild-type controls. We have concluded that TGF-beta1 regulates inflammation through the complex cytokine network and may be useful for the treatment of human uveitis. Other cytokines and inflammatory mediators may also be beneficial for therapy. Nitric oxide protects against ocular Toxoplasma gondii and limits the immune response. IL-12 inhibits EIU. Specimens from human ocular tissues with various diseases, including uveitis, retinal and corneal diseases, tumors, and metabolic genetic disorders, are studied by using routine histological, immunohistochemical, and in situ hybridization techniques. In uveitis, immunocompetent cells and cytokines, in addition to the stimulators (e.g., infectious organisms), are valuable adjuncts for making a clinical diagnosis and understanding the pathogenesis of the diseases. Elevation of IL-10 in the vitreous helps to diagnose intraocular large B-cell lymphoma, which frequently masquerades as idiopathic uveitis. We have reported that metastatic choroidal bacterial abscess occurs in AIDS, and the thickened cell wall structure of Propionibacterium acnes may relate to the resistance of bacterial killing and degradation by the host neutrophils and macrophages. Elucidating the immunopathological role of the relationship between the infiltrating cells and ocular resident cells will help us gain a better understanding and management of various ocular diseases in patients.

免疫活性细胞的身份和拓扑定位， 动物眼常驻细胞标志物的变化 采用免疫组织化学方法对各种实验性葡萄膜炎进行分析 和原位杂交。 在此之前，我们已经证明了T 淋巴细胞，特别是CD4细胞，是主要的 实验性自身免疫性葡萄膜视网膜炎（EAU）中的浸润细胞， 实验性黑色素蛋白诱导的葡萄膜炎（EMIU），但这两个巨噬细胞 中性粒细胞是主要的浸润细胞 在内毒素诱导的葡萄膜炎（EIU）和所有类型的白细胞， 存在于小鼠实验性睑缘炎中。 细胞因子（例如， 淋巴因子）和炎症介质（例如，一氧化氮）发挥作用， 在葡萄膜炎的免疫发病机制中起重要作用。 表达 主要组织相容性II类抗原和粘附分子 在炎症过程中在眼驻留细胞上观察到。 我们研究了转化生长因子-β（TGF-β 1）， 调节啮齿动物EMIU、鼠EIU和 TGF-β 1转基因小鼠。 TGF-β 1通过以下途径抑制EMIU复发 Th1细胞因子向Th2细胞因子的转变。 全身性TGF-β 1抑制EIU 和血清IL-6水平。 进行性白内障和一过性视网膜水肿 在TGF-β 1转基因小鼠中发育。 无显著 在EIU的诱导中，转基因组和非转基因组之间存在差异。 小鼠和野生型对照。 我们得出结论，TGF-β 1 通过复杂的细胞因子网络调节炎症， 用于治疗人葡萄膜炎。 其他细胞因子和 炎性介质也可能有益于治疗。 一氧化氮 保护眼睛免受弓形虫感染并限制免疫反应。 IL-12抑制EIU。 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 疾病，通过使用常规组织学， 免疫组织化学和原位杂交技术。 在葡萄膜炎中， 免疫活性细胞和细胞因子 (e.g.,感染性微生物），是进行临床 诊断和了解疾病的发病机制。 高程 白细胞介素-10在玻璃体中的表达有助于诊断眼内大B细胞 淋巴瘤，经常伪装成特发性葡萄膜炎。 我们有 报道了转移性脉络膜细菌性脓肿发生在艾滋病， 痤疮丙酸杆菌细胞壁增厚可能与 宿主对细菌杀灭和降解的抗性 中性粒细胞和巨噬细胞。 阐明免疫病理学作用 浸润细胞与眼驻留细胞的关系 将有助于我们更好地了解和管理各种眼 患者的疾病。