Mechanisms of Ocular Immune Privilege in the Posterior Eye

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DESCRIPTION (provided by applicant): Immune privilege is conserved in all species as a mechanism to provide immunoprotection for organs and tissues. Immune privilege allows for immune protection in the absence of inflammation. When immune privilege is compromised, the eye is at risk for immune inflammatory and autoimmune diseases such as uveitis. Immune privilege is a multi-layered process and even during experiment autoimmune uveitis, immune privilege is only transiently lost, and returns to prevent a reoccurrence of the disease (1). However, our studies show that retinal laser burn (RLB) in one eye caused an extended loss of ocular immune privilege in both the laser treated and non-treated eye (2). In this R21 project we would like to exploit these observations and analyze the mechanisms that led to the abrogation of immune privilege. We propose that RLB abrogates immune privilege by inducing changes to the retinal- pigmented epithelium (RPE) and its suppressor function which in turn leads to increased susceptibility to experimental autoimmune uveitis (EAU). Our research plan will 1.) Analyze how and what RPE suppression function is lost; 2.) Compare changes in the expression of candidate regulatory molecules on RPE that might change during or after RLB; 3.) Determine if there is increased susceptibility to autoimmune uveitis in mice after RLB. PUBLIC HEALTH RELEVANCE: This R21 application will determine (using state of the art cellular, molecular approaches) how experimental retinal laser burn abrogates immune privilege in the posterior eye. The knowledge gained from these studies will enhance our understanding of ocular immune homeostasis and may aid in the development of new therapies for restoration of the immune privileged status in eyes that suffer from trauma or inflammatory diseases such as autoimmune uveitis.