Anterior uveitis designates a collection of different diseases each characterized by a leukocyte infiltrate within the eye. The iris vascular endothelium acts as a gatekeeper to allow these cells to migrate into the anterior chamber of the eye. First, we propose to use iris rhodamine angiography to characterize leukocyte rolling, sticking, and diapedesis in the normal and inflamed eye. This characterization will include comparing different models of anterior uveitis, contrasting different cell subsets, quantitating the role of specific cytokines, and testing the role of specific adhesion molecules. Second, we hypothesize that the iris microvascular endothelium is unique relative to other endothelia. To test this we will establish cultures of iris microvascular endothelial cells, compare these functionally to cultures of microvascular endothelia from other tissues, and use differential mRNA display to identify unique gene products. Finally, we hypothesize that leukocytes from patients with anterior uveitis selectively bind to iris microvasculature more than leukocytes from normal controls. This hypothesis will be tested with leukocytes from patients with anterior uveitis by Woodruff-Stamper adhesion assays and iris angiography in SCID mice. These studies should clarify the role of the vascular endothelium in anterior uveitis. The studies have the potential to lead to novel, less toxic therapies for anterior uveitis.
