Fc gamma Receptors & Herpes Stromal Keratitis

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DESCRIPTION (provided by applicant): Prior studies in our laboratory have demonstrated that passive transfer of low dose monoclonal antibody to viral glycoproteins given after HSV-1 corneal infection can prevent the establishment of permanent blinding corneal inflammation. How antibody exerts its protective effect is not known. However, since no protection was seen when virus neutralizing F(ab)2, fragments were given in place of intact antibody Fc gamma receptors (FcgammaRs) were though to be involved. Recent advances have led to a fundamental revision of the significance of FcgammaRs. Two types are now recognized - those that when ligated activate cells and those which inhibit cell activation. Where both types are expressed by the same cell the net cellular response triggered by co-ligation is thought to depend on the ratio of expression of the two opposing signals. We will use wildtype and FcgR gene knockout mice to test the premise that viral antigen:antibody complexes via co-ligation favor negative FcgR signaling, and so suppress herpes stromal keratitis development. Our studies will provide new information on the expression and function of FcgammaRs in ocular tissue and may lead to novel strategies for controlling corneal inflammation.