Ophthalmic Research Lecture ‐ Role of the vascular endothelial cell in uveitis

Abstract

AbstractOf all the forms of inflammatory eye disease, posterior uveitis is the most likely to result in irreversible loss of vision. This disease results from: autoimmune disease; infection, most commonly toxoplasmosis; and in rare cases, B cell lymphoma. Patients with posterior uveitis frequently demonstrate clinical involvement of the retinal vasculature. Studies of rodent experimental autoimmune uveoretinitis conducted by other groups show that the lymphocytes that control this disease model access the retina via the retinal blood vessels. We have developed methods to isolate vascular endothelial cells from the retina of human cadaver donors; lymphocytes migrate readily across monolayers of these cells. In separate studies, we have observed that in comparison to other endothelial cell subtypes, retinal endothelial cells are relatively susceptible to infection with Toxoplasma gondii tachyzoites; increased binding of tachyzoites to the retinal endothelium may contribute to this susceptibility. We have also detected the expression of B cell lymphoid chemokines by vascular endothelial cells, as well as malignant lymphocytes, in primary central nervous system B cell lymphoma. Profiling analyses of the human retinal vascular endothelial cell, using gene expression microarray and shotgun proteomics, may help to clarify the molecular mechanisms that mediate interactions between the retinal vascular endothelium and lymphocytes or microbes in posterior uveitis. As the “gate” of the retina in posterior uveitis, the retinal endothelial cell holds much promise as a target for highly specific therapies of this disease.