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
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