Epidemic keratoconjunctivitis is a common human malady with the potential for prolonged ocular discomfort and impaired vision due to a chronic, multifocal, superficial stromal keratitis. Topical corticosteroids suppress the keratitis, but recurrences are common when corticosteroid therapy is withdrawn. Despite the identification over forty years ago of a specific adenovirus serotype as the etiologic agent of epidemic keratoconjunctivitis, today no specific therapy exists to prevent the debilitating corneal manifestations of the disorder. Based on existing evidence, we hypothesize that the corneal immunopathology in epidemic keratoconjunctivitis results from a cascade of events beginning with adenoviral infection of human corneal epithelium. In this proposal, we outline four separate but inter-related projects to test our hypothesis.
Our specific aims are: 1) to develop in vitro tissue culture models of human corneal infection by adenoviruses; 2) to elucidate the afferent arm of the host immune response to adenoviral infection in vitro; 3) to examine the efferent arm of the host immune response to adenoviral infection in vivo; 4) to develop a more physiologic animal model of adenovirus keratitis. A detailed understanding of the interactions between adenoviruses, the human cornea, and host immunity should lead to novel approaches to the prophylaxis and treatment of epidemic keratoconjunctivitis. The National Eye Institute, in its National Plan: 1994-1998 (p. 132), expressly identified study of """"""""the molecular genetic basis for inflammatory reactions within the cornea"""""""" as a program objective. In this Mentored Clinical Scientist Development Award proposal, we present a sequence of didactic course work (Phase I) and bench research (Phase II) designed to develop the Principle Investigator into an independent scientist with special expertise in viral immunology of the cornea.
