Posterior uveitis is a heterogeneous group of potentially blinding inflammatory disorders that primarily involve the retina and/or choroid. While different subtypes of posterior uveitis are known to be autoimmune, infectious and neoplastic, the basic pathogenic mechanisms responsible for these diseases remain unclear. Consistent with recent recognition that different vascular beds throughout the body are characterized by specific sets of cell adhesion molecules and chemoattractants, we hypothesize that the key to understanding the pathogenesis of posterior uveitis, and to developing effective therapeutic interventions, is defining the unique set of molecular signals expressed by retinal microvascular endothelium. Using unique, donor-matched, ocular vascular endothelial cell cultures and cDNA microarray technology, the investigators will study expression of over 8,000 genes by retinal endothelium, under different conditions of stimulation, and in comparison to gene expression by iris and choroidal endothelium. In addition, the investigators will make use of two retinal endothelial cell """"""""probes"""""""", namely, Toxoplasma gondii tachyzoites, infectious forms of a protozoan parasite that preferentially infect the retina, and malignant B cells from patients with primary central nervous system lymphoma, a tumor that also preferentially involves retina. Novel assays will be employed to investigate specificity of binding to, and isolate potential receptors for, these microbes and lymphocytes on retinal vascular endothelium. It is anticipated that these studies will provide new information about the mechanisms that are responsible for homing of leukocytes and microrganisms to the eye in posterior uveitis. This understanding may direct the development of new treatments for posterior uveitis that target specific interactions between the retinal microvascular endothelium and the infiltrating cell or invading microbe. The studies should also have implications for unrelated diseases affecting the retinal circulation, as well as tissue-specific inflammations and infections at other body sites. ? ?
Showing the most recent 10 out of 11 publications
