Although Staphylococcus aureus occupies a dominant position in external diseases of the eye, little is known about the relationship of the host to this important pathogen. Work supported by this grant has enabled us to develop rabbit models of blepharitis and corneal phlyctenules and catarrhal infiltrates related to S. aureus. We have shown that there is a hypersensitivity component to these diseases and that ribitol teichoic acid (RTA), a component of the cell wall of S. aureus and its major antigenic determinant, was the relevant antigen involved in their immunopathogenesis. Our results also suggested that antibody rather than delayed hypersensitivity to RTA appeared to be the mechanism involved in the immunopathogenesis of these diseases. Our grant proposal continues to focus on the host response to S. aureus with the following specific aims: 1. Determination of antibody levels to RTA in rabbit corneas. Using an enzyme-linked immunosorbent assay (ELISA), we will measure corneal antibody levels to RTA after various immunization schemes. Measuring corneal antibody levels to RTA may enable us to unravel the immunopathogenesis of hypersensitivity lesions of the cornea. 2. Identification of RTA in rabbit corneas with phlyctenules or catarrhal infiltrates and rabbit lids with blepharitis using the sensitive immunohistochemical avidin-biotin immunoperoxidase technique. 3. Use of ELISA to measure antibody levels to RTA in the case of S. aureus endophthalmitis or glycerol teichoic acid in the case of S. epidermidis endophthalmitis in rabbit aqueous and vitreous humor and serum to assess their diagnostic value. 4. Effect of antibodies to RTA on the viability of S. aureus. Al- though we have demonstrated the importance of antibodies to RTA in the development of hypersensitivity diseases of the cornea and lid, we have not explored the effect of these antibodies in host defense against S. aureus, i.e., do they enhance the ability of the host to destroy this pathogen. 5. Use of ELISA to measure antibody titers to RTA in serum and tears from patients with blepharitis and corneal phlyctenules and catarrhal infiltrates related to S. aureus to determine if our animal models have any relevance to human disease. The studies proposed in this grant may enable us to work out the immunopathogenesis of hypersensitivity diseases of the external eye related to S. aureus. Ultimately, the immunologic tests that we develop may have diagnostic potential for humans with hypersensitivity diseases of the external eye or endophthalmitis related to Staphylococcus.
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