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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004715-03
Application #
3259160
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1983-03-01
Project End
1986-02-28
Budget Start
1985-03-01
Budget End
1986-02-28
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of South Carolina at Columbia
Department
Type
Schools of Medicine
DUNS #
111310249
City
Columbia
State
SC
Country
United States
Zip Code
29208
Lawrence, A; Fox, K; Fox, A et al. (1992) Polypeptide profiles of normal and inflamed rabbit aqueous humor: identification of catabolic products of immunoglobulin G in the normal eye. Exp Eye Res 54:501-7
Fox, A; Fox, K (1991) Rapid elimination of a synthetic adjuvant peptide from the circulation after systemic administration and absence of detectable natural muramyl peptides in normal serum at current analytical limits. Infect Immun 59:1202-5
Fox, A (1990) Role of bacterial debris in inflammatory diseases of the joint and eye. APMIS 98:957-68
Kufoy, E A; Fox, K; Fox, A et al. (1990) Modulation of the blood-aqueous barrier by gram positive and gram negative bacterial cell wall components in the rat and rabbit. Exp Eye Res 50:189-95
Kufoy, E A; Pakalnis, V A; Parks, C D et al. (1989) Keratoconjunctivitis sicca with associated secondary uveitis elicited in rats after systemic xylazine/ketamine anesthesia. Exp Eye Res 49:861-71
Christensson, B; Gilbart, J; Fox, A et al. (1989) Mass spectrometric quantitation of muramic acid, a bacterial cell wall component, in septic synovial fluids. Arthritis Rheum 32:1268-72
Gilbart, J; Fox, A (1987) Elimination of group A streptococcal cell walls from mammalian tissues. Infect Immun 55:1526-8
Gilbart, J; Wells, A F; Hoe, M H et al. (1987) Sedimentation field flow fractionation and gas chromatography-mass spectrometry for characterization of streptococcal cell wall particles. J Chromatogr 387:428-33
Wells, A; Pararajasegaram, G; Baldwin, M et al. (1986) Uveitis and arthritis induced by systemic injection of streptococcal cell walls. Invest Ophthalmol Vis Sci 27:921-5
Eudy, L W; Walla, M D; Morgan, S L et al. (1985) Gas chromatographic-mass spectrometric determination of muramic acid content and pyrolysis profiles for a group of gram-positive and gram-negative bacteria. Analyst 110:381-5

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