CELL ADHESION MOLECULES IN OCULAR INFLAMMATION

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Cell adhesion molecules are surface proteins that mediate the binding of cells to extracellular matrix and to other cells. The expression of cell adhesion molecules, which is important for the migration of leukocytes to sites of inflammation, is partly regulated by the secretion of cytokines. We are studying the expression of cell adhesion molecules in ocular inflammation and investigating the blocking of cell adhesion molecules as a treatment for uveitis and other ocular inflammatory diseases. Over the past year we have shown that treatment with a monoclonal antibody against Mac-1 inhibits the development of endotoxin-induced uveitis in mice. We later demonstrated that monoclonal antibodies blocking intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) inhibits the development of both endotoxin-induced uveitis in rats and experimental autoimmune uveitis in mice. These antibodies against ICAM-1 and LFA-1 also inhibited lymphocyte stimulation in vitro. Finally, studies of expression of cell adhesion molecules in animal models of uveitis have shown that ICAM-1 is expressed in the eye before the infiltration of inflammatory cells. In studies of human biopsy tissue, we demonstrated the expression of ICAM-1, E-selectin, and vascular cell adhesion molecule-1 (VCAM-1) in corneal graft failure. The strongest expression of ICAM-1 occurred in corneal specimens with the greatest inflammatory disease, suggesting that cell adhesion molecule expression plays a role in corneal graft failure. We previously had demonstrated the expression of cell adhesion molecules in human eyes with posterior uveitis and the expression of E-selectin in the anterior segment of animal eyes with endotoxin-induced uveitis.