Investigator's description): Onchocerciasis (river blindness) is a leading cause of infectious blindness and visual impairment world-wide. Sclerosing keratitits develops as a result of the host immune response to degenerating microfilariae in the corneal stroma. As eosinophils are prominent components of the cellular infiltrate associated with the onchocercal keratitis, the goal of this proposal is to examine the molecular basis for eosinophil recruitment, degranulation and cytotoxicity in a murine model of O. volvulus mediated keratitis.
Aim 1 will test the prediction that IL-5 and eotaxin are required for recruitment of eosinophils into the corneal stroma during O. volvulus mediated keratitis by antibody neutralization and utilization of IL-5 gene knockout mice.
Aim 2 will examine the role of ICAM-1, ICAM-2 and VCAM-1 and the counter-receptors LFA-1 and VLA-4 in eosinophil recruitment in both immunocompetent and IL-4 gene knockout mice (which do not develop keratitis).
Aim 3 will determine the roles of IgE and IgG in eosinophil degranulation and cytotoxicity by examining surface expression of IgE and IgG on eosinophils in situ, and by utilizing murine IgE and IgG Mabs to induce degranulation and cytotoxicity both in vitro in corneal cell culture and in vivo. These studies are intended to enhance the understanding of the immunopathology of onchocercal keratitis and other eosinophil mediated forms of keratitis.
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