Infiltration of neutrophils and eosinophils from the limbal vessels to the corneal stroma involves adherence to vascular endothelial cells, and transmigration across this cell layer into the corneal stroma. The composition of the inflammatory cell infiltrate depends on the selective expression of vascular cell adhesion molecules, and on production of specific chemotactic stimuli.
The Specific Aims outlined in this proposal are focused on determining the molecular basis for immune-complex mediated recruitment of neutrophils and eosinophils to the cornea in a murine model for Onchocerca volvulus keratitis (river blindness). The proposed studies will assess the role of C5a, and. will determine if Fc gamma receptor expression is required for production of chemotactic and immunoregulatory cytokines by neutrophils and eosinophils in the cornea, including KC, MIP-2, MIP-1 alpha, eotaxin, RANTES, TNF-alpha, IFN-gamma, and IL-4. Studies will also determine the relative importance of vascular cell adhesion molecules PECAM-1, VCAM-1, ICAM-1 and P-selectin in recruitment of these cells. The long-term goal of these studies is to identify potential targets for immune based therapy that can be applied to O.volvulus keratitis and to other ocular conditions in which neutrophils or eosinophils are predominant, such as herpes simplex keratitis and ocular allergy.
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