IMMUNOPATHOLOGY IN EYES WITH EXPERIMENTAL AND CLINICAL OCULAR DISEASES

应用免疫组织化学、原位杂交、聚合酶链反应（PCR）和显微切割技术，对各种实验性葡萄膜炎动物眼内免疫活性细胞的身份、局部定位和细胞标志物的变化进行了分析。以前，我们已经证明，T淋巴细胞是实验性自身免疫性葡萄膜视网膜炎和实验性黑色素诱导的葡萄膜炎的主要浸润细胞，巨噬细胞和多形核中性粒细胞是内毒素诱导的葡萄膜炎的主要浸润细胞，而所有类型的白细胞都存在于小鼠实验性睑缘炎。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。主要组织相容性（MHC）II类抗原，粘附分子和凋亡标志物的表达在炎症过程中观察到的眼驻留细胞。在1998财政年度，我们已经确定了动力学的Th 1和Th 2细胞因子，凋亡分子Fas，FasL，bcl-2和Bax的眼睛的动物模型和人类标本与葡萄膜炎。利用显微切割和PCR，我们已经确定了免疫球蛋白重链基因重排和bcl-2易位在原发性眼内淋巴瘤细胞在体内。这些淋巴瘤细胞还在玻璃体中产生IL-10 mRNA和IL-10，这可以帮助诊断。我们已经证明，在视网膜血管瘤中的泡沫状基质细胞的VHL（VHL）疾病有VHL基因，一种肿瘤抑制基因的丢失。因此，它减少正常VHL蛋白的翻译，干扰延长蛋白和诱导血管内皮生长因子，促进新血管形成。显微切割和分子生物学技术的结合有助于我们研究选择性微小细胞群及其遗传学。阐明浸润细胞和眼部驻留细胞之间的关系的免疫病理学作用将有助于更好地理解和管理患者的各种眼部疾病。- 免疫病理学，眼，葡萄膜炎，淋巴瘤，分子病理学-人类受试者

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