A dominant role for Fc gamma receptors in antibody-dependent corneal inflammation

Although production of specific Ab is a critical element of host defense, t he presence of Ab in tissues leads to formation of immune complexes, which can trigger a type Ell Arthus reaction. Our studies on a mouse model of riv er blindness showed that Ab production is essential for recruitment of neut rophils and eosinophils to the cornea and for development of corneal opacif ication. In the current study, we determined the relative contribution of c omplement and Fc gammaR interactions in triggering immune complex-mediated corneal disease. Fc gammaR(-/-) mice, C3(-/-) mice, and immunocompetent con trol (B6/129Sj) mice were immunized s.c. and injected intrastromally with O nchocerca volvulus Ags. Slit lamp examination showed that control mice, C3( -/-) mice, and control mice injected with cobra venom factor developed pron ounced corneal opacification, whereas corneas of Fc gammaR(-/-) mice remain ed completely clear. Furthermore, recruitment of neutrophils and eosinophil s to the corneal stroma was significantly impaired in Fc gammaR(-/-) mice, but not in C3(-/-) mice or cobra venom factor-treated mice. We therefore co nclude that Fe gammaR-mediated cell activation, rather than complement acti vation, is the dominant pathway of immune complex disease in the cornea. Th ese findings demonstrate a novel role for Fc gammaR interactions in mediati ng ocular inflammation.