PURPOSE: This study was designed to investigate an animal model of uveitis that resembles anterior uveitis in humans after immunization with iris-ciliary body antigen. METHODS: Male Lewis rats 6 to 8 weeks of age were immunized with the buffer- and detergent-insoluble bovine iris-ciliary body antigen mixed with complete Freund's adjuvant and pertussis toxin. Antigen was digested with various proteolytic enzymes and tested in different rodent strains for a uveitogenic response. RESULTS: Acute iridocyclitis developed in both eyes of the Lewis rat during the second week after immunization, and the pattern of inflammation was similar to acute anterior uveitis in humans, with sudden onset, localization to the anterior uvea, and spontaneous resolution. Among the strains tested, F344 rats were susceptible to experimental autoimmune anterior uveitis but Long-Evans rats were not. Experimental autoimmune anterior uveitis did not develop in any of the mice studied, nor was it induced by immunization with synthetic melanin, amelanotic bovine tissues, pigmented bovine skin, or pigmented rat and rabbit iris-ciliary body. A soluble fraction derived from bovine melanin-associated antigen (BMAA) after digestion with the proteolytic enzyme V8 protease resulted in a disease similar to that observed with intact BMAA. CONCLUSIONS: A model of anterior uveitis has been induced in the Lewis rat after immunization with bovine uveal antigen, and it resembles the acute iridocyclitis observed in humans. These results suggest that the pathogenic antigen is a melanin-associated protein(s) present within the iris-ciliary body.
PURPOSE: This study was designed to investigate an animal model of uveitis that resembles anterior uveitis in humans after immunization with iris-ciliary body antigen. METHODS: Male Lewis rats 6 to 8 weeks of age were immunized with the buffer- and detergent-insoluble bovine iris-ciliary body antigen mixed with complete Freund's adjuvant and pertussis toxin. Antigen was digested with various proteolytic enzymes and tested in different rodent strains for a uveitogenic response. RESULTS: Acute iridocyclitis developed in both eyes of the Lewis rat during the second week after immunization, and the pattern of inflammation was similar to acute anterior uveitis in humans, with sudden onset, localization to the anterior uvea, and spontaneous resolution. Among the strains tested, F344 rats were susceptible to experimental autoimmune anterior uveitis but Long-Evans rats were not. Experimental autoimmune anterior uveitis did not develop in any of the mice studied, nor was it induced by immunization with synthetic melanin, amelanotic bovine tissues, pigmented bovine skin, or pigmented rat and rabbit iris-ciliary body. A soluble fraction derived from bovinemelanin-associated antigen (BMAA) after digestion with the proteolytic enzyme V8 protease resulted in a disease similar to that observed with intact BMAA. CONCLUSIONS: A model of anterior uveitis has been induced in the Lewis rat after immunization with bovine uveal antigen, and it resembles the acute iridocyclitis observed in humans. These results suggest that the pathogenic antigen is a melanin-associated protein(s) present within the iris-ciliary body.