Endotoxin-induced uveitis in rats as a model for human disease

Acute anterior uveitis is a relatively common disease of uncertain aetiology. Its association with a wide variety of systemic disorders including ankylosing spondylitis, Reiter's syndrome, Behçet's disease, juvenile rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease and sarcoidosis and the prevalence of the HLA antigen B27 (ref. 1) in cases without associated disease have been noted but not explained. In general, animal models for uveitis have not clarified the mechanism of human disease. Most require direct intravitreal injection² or repeated immunizations with retinal or uveal antigens³. Uveitis does occur in adjuvant arthritis, a syndrome that can be produced in rats by the systemic injection of pepti-doglycan from the cell wall of a variety of Gram-positive bacteria⁴. The disease, which was initially described following the injection of mycobacteria in mineral oil, has many similarities to Reiter's syndrome⁵, including the development of eye pathology in as many as 40% of the animals⁶. As Reiter's syndrome is associated with enteric Gram-negative infections such as Shigella, Salmonella and Yersinia, we sought to produce an arthritis in rats by injecting killed Gram-negative bacteria. Although we have not observed clinical arthritis in these animals, careful histological study has shown the near-universal appearance of uveitis. The studies described below indicate that the eye disease is due to a portion of the bacterial cell wall known as endotoxin or lipopolysaccharide (LPS).