Thymic Expression Of Ocular Proteins--Autoimmune Uveitis

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Experimental autoimmune uveitis (EAU) is a well established model of human intraocular inflammatory diseases or uveitis and is easily induced in susceptible animal species by immunization with retinal proteins, such as interphotoreceptor retinoid binding protein (IRBP) and S-Antigen (SAg). Marked differences exist among different animal species and strains in their susceptibility to EAU induction but the cause for these differences is not completely clear. Mice are generally resistant to EAU while most rat strains are susceptible. Knowledge about the basic mechanisms underlying resistance to EAU or tolerance induction to ocular proteins may prove beneficial for the treatment or prevention of ocular inflammatory diseases. In FY 1996-1997 we demonstrated that there is strong correlation between constitutive expression of ocular autoantigens in the thymus (mRNA and protein) and resistance to EAU. This correlation was noted both at the species (mice vs. rats or monkeys) and sub-species levels (differences among strains). In 1997-1998 fiscal year we found that SAg is expressed in human thymi and may therefore serve as a useful indicator of susceptibility to uveitis. We have now extended this analysis to other retinal proteins known to induce uveitis in rodents. These results reveal that in addition to SAg, IRBP, opsin and recoverin are expressed in the human thymus. However, there is significant variability in the level of expression of these antigens in an individual and in the population. Significant effort is now directed at developing non-invasive methods of obtaining thymic biopsy and sensitive real-time RT-PCR assays to quantify levels of thymic expression of putative autoantigens. The goal is to quantify risk of developing any organ-specific autoimmune disease.