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.