Experimental autoimmune anterior uveitis (EAAU). III. Induction by immunization with purified uveal and skin melanins.

The pathogenicity of uveal tissue and melanin has been a controversial subject for a long time. The present new approach has elucidated some of the problems. Melanin granules have been extracted from bovine choroid, iris, hair and skin, and from human, monkey and rabbit choroid. The melanin granules have further been purified by detergent extractions, and are free from pathogenic retinal antigens. Lewis rats immunized with microgram doses bovine choroidal or iris melanin-protein (in Freund's complete adjuvant or Hunter's adjuvant, combined with pertussis toxin) develop severe experimental autoimmune anterior uveitis (EAAU). No retinitis or pinealitis is found. The other melanins are weakly uveitogenic or inactive. The relative pathogenicity of the various melanins seems to be related to tissue and species specificity. The responsible hypothetic pathogenic structure UP-X (uveal pathogen X) is highly stable and resists proteolytic digestion by various enzymes. Its pathogenic activity is destroyed by hot 6 N HCl or longlasting 0.5 N NaOH treatment. In view of its chemical and immunological features it is probably identical to the pathogen PEP-X of bovine retinal pigment epithelial melanin. UP-X-induced EAAU can be transferred by spleen cells, and is suppressed by cyclosporin showing that a T-cell-mediated pathogenic mechanism predominates. It resembles human anterior uveitis by its specific location, its transient nature, and sparing of the retina. In these respects EAAU differs from retinal photoreceptor antigen-induced forms of EAU where retinitis with photoreceptor damage is a main feature. The involvement of melanin in human ocular diseases is discussed.