Endotoxin, a major component of the outer cell wall of gram negative bacteria, induces acute onset anterior uveitis, similar to that seen in humans with HLA-B27 when it is injected subcutaneously into rodents. To clarify the pathogenesis of endotoxin-induced uveitis and relate it to HLA-B27-associated disease, the investigators plan to: (1) use mice with genetic alterations rendering them unable to elaborate specific cytokines or functional cytokine receptors as a means of defining the role of these cytokines in response to endotoxin-induced eye inflammation; (2) use mice with genetic deficiencies in specific adhesion molecules to define the role of these ligands in endotoxin-induced uveitis; (3) use rats raised in a sterile environment to determine if the lesser degrees of endotoxin-induced uveitis seen with progressive age results from chronic exposure to endotoxins; and (4) characterize a newly-described rat model of HLA-B27-associated uveitis subsequent to challenge with live Salmonella or Yersinia. This characterization of uveitis in transgenic HLA-B27 rats will permit studies on the relationship between HLA-B27, gram negative bacteria, and iritis. When taken together, the specific aims are designed to help clarify the pathogenesis of the anterior uveitis.
