Although Staphylococcus aureus and epidermis are important and common bacterial causes of ocular disease, little is known about the ocular immune response to these organisms. In addition to destruction caused by proliferating S. aureus and its toxins, hypersensitivity to this organism may be associated with blepharitis and corneal phlyctenules and catarrhal infiltrates. Our rabbit models of staphylococcal endophthalmitis and hypersensitivity diseases have enabled us to study the immune response associated with these important diseases. This grant continues to focus on our animal models of human disease and has two major specific aims: (1) treatment of staphylococcal blepharitis and corneal hypersensitivity lesions using Staphage Lysate (SPL) and (2) the immune response to staphylococcal endophthalmitis in the rat. There is renewed interest in using SPL to treat resistant cases of staphylococcal blepharitis and corneal hypersensitivity lesions in humans. Before human studies, it would be reasonable to test SPL in our rabbit model to determine: (1) the effect of SPL injections on delayed-type hypersensitivity (DTH) to S. aureus (measured by skin tests) and antibody titers (measured by ELISA) in serum, tears and corneas of normal rabbits, (2) the effect of SPL on DTH and antibody titers in our rabbit model of staphylococcal blepharitis and corneal hypersensitivity lesions, and (3) the impact of SPL on the development and evolution of blepharitis and corneal hypersensitivity lesions. Except for our studies of S. aureus endophthalmitis and S. epidermis endophthalmitis in rabbits, there have been no reports examining the immune response to staphylococcal endophthalmitis or, for that matter, to any type of bacterial endophthalmitis which is a devastating disease in humans. Since the rat immune system is much better defined than the rabbit, we would like to pursue future studies in Lewis rats. Proposed studies are directed at both the systematic and ocular immune response to staphylococcal endophthalmitis and include: studies of cell- mediated immunity to staphylococcal antigens using skin tests for DTH and lymphocyte proliferation assays; studies of humoral immunity to staphylococcal antigens using an ELISA to measure antibody levels in blood; immunohistochemistry to characterize changes and orientation of lymphocyte phenotypes in lymph nodes and spleen cell sorting analysis to characterize changes in lymphocyte phenotypes in blood, lymph nodes spleen; and studies of the time course of development of endophthalmitis in the rat eye, using immunohistochemistry to characterize leukocytes infiltrating cytokine and antibody measurements in vitreous, and correlation of the immune response with clinical observations, culture results and gross and histopathologic findings. Athymic nude rat will allow us to determine the importance of T cells. These studies should enable us to characterize for the first time the immune response to staphylococcal endophthalmitis, the most important cause of postoperative bacterial endophthalmitis in humans.
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