The identity and topographic localization of immunocompetent cells and the alteration of surface markers on ocular resident cells and their cytokines in animals with experimental autoimmune uveoretinitis or endotoxin-induced uveitis (EAU, EIU) and in human ocular tissues with various diseases were analyzed by immunohistochemical studies and in situ hybridization. T lymphocytes were the predominant infiltrating cells in EAU, yet both macrophages and polymorphonuclear neutrophils (PMNs) were the predominant infiltrating cells in EIU. Migration of the inflammatory cells from the vessels into the target site is directed by adhesion molecules, which can be expressed on vascular endothelium and other resident cells in the eye. Mast cells appear to participate in the immunopathogenesis of EAU and EIU. T-lymphocyte specificity is directed to small fragments of antigen bound to cell surface major histocompatibility complex (MHC) molecules, which are presented on the surface of specialized antigen-presenting cells. The expression of MHC class-II antigens was observed on ocular resident cells such as retinal pigment epithelium (RPE), retinal endothelium, keratocytes, fibroblasts, and ciliary epithelium in rodents. Both the infiltrating cell subpopulation and the expression of class-II antigens and adhesion molecules on ocular resident cells can be altered by various immunomodulating agents and cytokines. Specimens from human ocular tissues with various diseases--such as uveitis, retinal disease, conjunctival and corneal diseases, metabolic genetic diseases, and tumors--are studied using immunohistochemical and in situ hybridization techniques as well as light and electron microscopic evaluation. In uveitis, immunocompetent cells and lymphokines are valuable adjuncts to clinical diagnosis, and they are determinants of disease course and prognosis. In nonuveitic conditions, alteration of cellular membrane surface markers and intracytoskeleton of the ocular resident cells may imply damage and abnormalities in these diseases. Elucidating the immunopathological role of the relationships between infiltrating inflammatory or malignant cells and other resident cells in the clinical behavior of various diseases will increase our understanding of human ocular disorders.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Intramural Research (Z01)
Project #
1Z01EY000222-08
Application #
3777628
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
1993
Total Cost
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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