IMMUNOPATHOLOGY IN EYES WITH EXPERIMENTAL AND CLINICAL OCULAR DISEASES

采用免疫组织化学、原位杂交、聚合酶链式反应和显微解剖等方法，对不同类型实验性葡萄膜炎动物眼内免疫活性细胞的定位、定位及细胞标志物的变化进行了分析。以前，我们已经证明在实验性自身免疫性葡萄膜炎和实验性黑素性葡萄膜炎中，T淋巴细胞是主要的浸润细胞，在内毒素诱导的葡萄膜炎中，巨噬细胞和中性粒细胞是主要的浸润细胞，而在小鼠的实验性眼睑炎中，所有类型的白细胞都存在。细胞因子和炎症介质在眼部炎症的免疫发病机制中起重要作用。在炎症过程中，眼部驻留细胞表达主要组织相容性II类抗原、黏附分子和凋亡标记物。在1998财年，我们在葡萄膜炎动物模型和人类标本中都发现了Th1和Th2细胞因子以及Fas、FasL、bcl2和bax等凋亡分子的动态变化。利用显微切割和聚合酶链式反应，我们已经在体内鉴定了免疫球蛋白重链基因重排和bcl2在原发眼内淋巴瘤细胞中的易位。这些淋巴瘤细胞还在玻璃体中产生IL-10mRNA和IL-10，有助于诊断。我们已经证实von Hippel-Lindau(VHL)病视网膜血管瘤中的泡沫基质细胞存在肿瘤抑制基因VHL的缺失。因此，它减少了干扰细长蛋白的正常VHL蛋白的翻译，并诱导血管内皮生长因子促进新生血管的形成。显微解剖和分子技术的结合有助于我们研究选择性的微小细胞群体及其遗传学。阐明浸润性细胞和眼部驻留细胞之间的免疫病理关系有助于更好地了解和处理患者的各种眼部疾病。-免疫病理学、眼部、葡萄膜炎、淋巴瘤、分子病理学-人类科目

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, polymerase chain reaction (PCR), and microdissection. 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, apoptotic molecules of 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 in vivo. 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. - immunopathology, eye, uveitis, lymphoma, molecular pathology - Human Subjects