The central hypothesis of this project is that chronic uveitis is both a cause and result of recurrent cycles of fibrin deposition and lysis within the eye, and that this process is modulated by the interactions of fibrinogen associated factors (FAF) with both tissue and inflammatory cell systems with the eye. Thus the project emphasizes fibrin metabolism in chronic uveitis and its complications.
Specific Aims are: 1. To visualize and quantify structural and antigenic distributions of fibrinogen associated factors (FAF) and other inflammatory systems in feline chronic mycobacterial-induced uveitis CMIU. 2. To quantitate the functional levels of FAF and other inflammatory systems at various stages of feline (CMIU). 3. To determine whether fibrin or other FAF are a cause or result of pathophysiology observed at various stages of CMIU. 4. To determine the role of the endocular procoagulant/fibrinolytic balance in CMIU. 5. To develop a murine model of CMIU and determine the role of FAF in murine CMIU. 6. To determine the endocular distribution of other inflammatory systems at various stages of murine CMIU. 7. To define the roles of known immunologic mechanisms in CMIU and FAF-mediated eye injury. Our approach will emphasize: a) correlalions of in vivo pathophysiological and in vitro immunopathological data, and b) progression from feline to more sophisticated murine model which allow elegant immunological techniques to define the mechanisms that govern the role of FAF in CMIU and like diseases. Clinical relevance of the study derived from a virtual absence of current studies of chronic uveitis mechanisms despite the lack of effective therapy; and from ignorance of the roles of fibrin and FAF as potential agents of chronic inflammation in many body regions incuding the eye.
