Uveitis is an inflammatory disease of unknown etiology. Uveitis and several related disorders, including Reiter's syndrome and ankylosing spondylitis show a high association with the histocompatibility antigen HLA-B27 and dysentery mediated by gram negative rods. A variety of bacterial products including endotoxin and Freunds complete adjuvant will elicit uveitis on systemic injection in animals. It is our hypothesis that uveitis in man results from an immunologic or toxic reaction to persisting bacterial debris disseminated to the eye from focal sites of infection. Certain bacterial cell walls possess the essential properties of toxicity and immunogenicity. Furthermore, they are poorly biodegradable and persist in tissues for long periods of time. We have recently developed a model of uveitis elicited by streptococcal cell wall fragments and propose to extend our studies on the relationship of the composition of peptidoglycan containing macromolecules isolated from gram positive, gram negative and acid fast organisms with their inflammatory properties, persistence and dissemination to ocular tissues. Our research plan is as follows: firstly, to attempt to elicit uveitis after systemic injection of cell wall fragments; secondly, to compare the inflammatory properties in the eye of cell wall debris differing somewhat in chemical and/or physical composition; thirdly, to determine the immunopathologic mechanisms of tissue damage induced by bacterial debris employing immunofluorescence procedures; and finally, to determine persistence and dissemination to ocular tissues of bacterial debris as determined by gas chromatography-mass spectrometry and solid phase radioimmunoassay. The work should provide fundamental information on the immunopathology of uveitis as well as allow the extension of this work to the direct testing of our hypothesis by measuring levels of bacterial debris and immune complexes in human ocular tissues and body fluids.
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