Inflammatory diseases of the cornea comprise the largest single cause of blindness in the world. The subset of peripheral ulcerative keratitis is an enormous problem. Adequate study of patients with peripheral ulcers (as seen, for example, in Mooren's ulcer, Wegener's granulomatosis, and rheumatoid arthritis or other collagen vascular diseases) is hampered from logistical and ethical considerations. Our lack of understanding of basic mechanisms, our inability to stop and the ulcerative process, and our inability to extensively study an animal model. The goal of the research described in this proposal is to develop a reproducible animal model of peripheral ulcerative keratitis in an inbred strain of guinea pigs (13/N). Three different immunologic approaches will be employed: 1) immunization with purified guinea pig and with bovine calf collagens (types I, III, and IV); 2) immunization with homologous ocular antigen preparations; 3) immunization with chemically altered homologous ocular antigens. We propose also to produce heavy chain-specific antibodies to guinea pig IgG, to guinea pig IgA and to guinea pig IgM. We believe the informaiton derived from these efforts to develop an animal model of peripheral ulcerative keratitis will provide some understanding of the pathogenic and effector mechanisms involved in production of the lesions. More importantly, such a model would provide the unique and valuable opportunity to study in detail the immunopathology and the response to various therapies.