Endotoxin-induced Uveitis Revisited

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Uveitis is a major cause of blindness. Anterior uveitis is approximately four times as common as posterior uveitis. Endotoxin-induced uveitis, a model first described by the PI nearly 30 years ago, has been a valuable tool to understand acute inflammation in the anterior uveal tract. In the last decade, the understanding of endotoxin-induced inflammation has been revolutionized with the characterization of the TLR4 receptor and the e merging clarification of the intracellular pathways activated by endotoxin. It is obviously critically important to relate this new understanding of endotoxin-related effects to the anterior uveal tract. Consequently we propose to 1) determine the relative importance in the iris/ciliary body of the two intracellular pathways known to be activated by endotoxin, MyD88 and TRIF and 2) compare and contrast the phenomenon of endotoxin tolerance when endotoxin is injected into mice intravitreally as opposed to intraperitoneally. These proposed studies will broaden the knowledge of the effects of endotoxin on the eye. Future studies can buil d on these observations to test anti-inflammtory molecules induced by endotoxin as these molecules are potentially useful in the treatment of uveitis and other inflammations.