Experimental autoimmune anterior uveitis (EAAU): induction by melanin antigen and suppression by various treatments.
The uveitogenicity of melanin has been a controversial subject for a long time, presumably as a result of the use of ill-defined preparations in the experiments. We have developed procedures for the preparation of purified uveitogenic melanins from the retinal pigment epithelium and choroid that are free from pathogenic retinal photoreceptor proteins. The active melano-antigen is located at the surface of the melanin granules and is probably identical in both tissues. It retains its pathogenicity in hot polar detergent and during in vitro proteolysis, but it is inactivated by macrophage phagocytosis and hydrolysis in hot hydrochloric acid. Lewis rats immunized with microgram doses of bovine retinal pigment epithelial or choroidal melanin develop severe experimental autoimmune anterior uveitis (EAAU) about 10 days later. Retinitis and pinealitis are not observed. Skin melanin prepared in a similar way evokes EAAU as well, but it is only weakly pathogenic. EAAU cannot be transferred by serum, and its development can effectively be inhibited by antibodies to the inciting antigen and by cyclosporin. Vitamin E treatment of the animals causes a delay in its onset. The results indicate that cell-mediated immunity plays a dominant role in the pathogenesis of EAAU. This is the first time it has been shown that purified ocular and skin melanins are able to induce an autoimmune disease. The relevance of this finding for the study of melanin-related immunopathology in man is discussed.
Institute of Ophthalmology, University of Nijmegen, The Netherlands.
R M
RM
Broekhuyse
E D
ED
Kuhlmann
H J
HJ
Winkens
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D000941:Antigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D002417:Cattle; D016572:Cyclosporine / Q000627:therapeutic use; D004195:Disease Models, Animal; D007167:Immunotherapy; D008543:Melanins / Q000276:immunology* / Q000302:isolation & purification; D010857:Pigment Epithelium of Eye / Q000276:immunology; D011817:Rabbits; D051381:Rats; D011917:Rats, Inbred Lew; D012867:Skin / Q000737:chemistry / Q000276:immunology; D014606:Uveitis, Anterior / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D014810:Vitamin E / Q000627:therapeutic use
D000906:Antibodies; D000941:Antigens; D008543:Melanins; D014810:Vitamin E; D016572:Cyclosporine