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. It is our hypothesis that uveitis in man results from an immunologic or toxic reaction to persisting bacterial debris disseminated to the eye from extraocular sites of infection such as the gut or elsewhere. Certain bacterial cell walls possess the essential properties of toxicity and immunogenicity. Furthermore, they are poorly biodegradable and may persist in certain tissues for long periods of time. We have determined that peptidoglycan-polysaccharide complexes (PG-PS) isolated from group A streptococci when injected intravitreally in the rabbit will elicit perpetuating uveitis. However, when injected intraperitoneally in the Lewis rat PG-PS elicts a self limiting bilateral uveitis with associated perpetuating polyarthritis. Our major goals are to attempt to understand the factors that determine how PG-PS and other bacterial debris initiate and maintain acute or chronic inflammation in the eye. We wish to obtain detailed information on relative distribution of different sizes of cell wall particles on systemic administration to animals as well as their subsequent elimination from these sites. Four separate but interrelated approaches will be taken a) solid phase enzyme immunoassay to measure levels to cell wall antigens b) fused silica capillary gas chromatography-mass spectrometry to measure levels of bacterial chemical markers c) sedimentation field flow fractionation to measure the particle size distribution of PG-PS in different tissues d) immunohistochemistry to determine the sites of localization of bacterial debris within various tissues. In addition we shall obtain further information on the enzymatic processes by which PG-PS is processed in relationship to ocular inflammation including studies with lysozyme and the more recently described N-acetyl muramyl L-alanine amidase. This work should provide important information on the mechanisms by which the processing of bacteria can lead to inflammatory diseases of the eye.
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