Local cyclosporine therapy for experimental autoimmune uveitis in rats.
The use of locally applied cyclosporine was investigated in the retinal S-antigen-induced experimental autoimmune uveitis (EAU) model in Lewis rats. A 2% cyclosporine solution applied topically four times a day for 14 days effectively prevented the expression of EAU. This treatment, however, produced circulating cyclosporine levels in the therapeutic range. Lower concentrations of cyclosporine applied topically did not produce therapeutic levels and were not capable of reliably preventing disease. Intraocular levels of cyclosporine, measured by radioimmunoassay, were extremely low and outside the accepted therapeutic range. Intravitreal cyclosporine therapy appeared to protect eyes from EAU, without producing significant circulating cyclosporine levels. These findings show that, in its present form, cyclosporine in oil is not an efficacious topical therapy. Therefore, a local cyclosporine preparation with enhanced penetration into the globe may be a practical approach to therapy in the future.
D000287:Administration, Topical; D000818:Animals; D000941:Antigens / Q000276:immunology; D019393:Arrestin; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003524:Cyclosporins / Q000378:metabolism / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005123:Eye / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D007114:Immunization; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D014018:Tissue Distribution; D014605:Uveitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D000941:Antigens; D019393:Arrestin; D003524:Cyclosporins