Uveitis is a group of inflammatory eye diseases that may result from infections, malignancies, trauma, or incompletely understood processes that are presumably mediated by the body's immune system. In many cases, uveitis is associated with underlying inflammatory disease processes elsewhere in the body. Uveitis may be also associated with multiple sclerosis (MS) where the central nervous system (CNS) inflammation is associated with the inflammation of the eye. In these studies, it is proposed to clarify the relationship between inflammation in the eye and in the CNS, which may give a clue about the mechanism of development of this inflammatory disease. It may also provide a useful model for studying an eye inflammation as a complication of human systemic disorders. For this reason, it is proposed to use an animal model for MS-EAE. Similarly to some patients with MS, animals develop inflammation of the eye that is associated with the inflammation of the spinal cord. In Lewis rats, uveitis can be re-induced with the second dose of myelin basic protein (MBP). Therefore, this animal model permits the study of the mechanism of relapsing uveitis, which in humans leads to permanent tissue damage and blindness. It is proposed to test the hypothesis that there are common pathogenic autoimmune mechanisms involved in inflammation of the eye and the CNS, including common target antigens. Thus, in the proposed model, MBP-specific T cells play a role in the initiation of the events leading to uveitis as well as in the recurrence of eye inflammation. The applicants hypothesize that not only the cells but also factors that attract those cells to the eye are important components of the pathogenic process. To elucidate the immunological mechanism involved in the pathogenesis of uveitis, they propose the following specific aims: (1) Determine specificity of the immune response for a target antigen in Lewis rats which develop both anterior uveitis and EAE after immunization with MBP. (2) Define the role of T cells in the recurrent uveitis in Lewis rats upon re-examination with MBP. (3) Examine the role of cytokines and chemokines in the recruitment of cell to the eye in primary and recurrent uveitis associated with EAE after immunization of Lewis rats with MBP.
