Uveitis, or ocular inflammation, is a blinding condition that affects around 300,000 people in the US, and millions world-wide. Chronic forms of uveitis are associated with poor visual outcomes and require long-term immune suppression therapy. Post-infectious uveitis is a devastating form of chronic uveitis that develops after an ocular or a systemic infection and is challenging to treat. There is a significant lack of understanding about the fundamental mechanisms responsible for post-infectious uveitis. This has limited the development of effective treatment strategies and new treatment options. Currently, there is debate whether post-infectious uveitis is caused by the presence of killed microbial antigens retained in the eye, or generated by an inadvertent autoimmune response triggered by infection. To answer this question, we developed a mouse model of chronic post-infectious uveitis termed primed mycobacterial uveitis (PMU). Our preliminary data show that the adaptive but not innate immune system is necessary for chronic uveitis, and supports an autoimmune mechanism of disease. In the current proposal we will extend our initial findings to build a more detailed understanding of the mechanisms responsible for post-infectious uveitis and test the hypothesis that chronic post-infectious uveitis results from a de novo T-cell mediated adaptive immune response to ocular antigens.
The mechanisms responsible for chronic post-infectious uveitis are not known. We propose to use a new mouse model, primed mycobacterial uveitis (PMU), to test the hypothesis that a de novo anti- ocular autoimmune response underlies chronic inflammation.
