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N. Kitaichi, K. Ohgami, T. Miura, S. Ohno; Amelioration of Experimental Autoimmune Uveoretinitis Treated With Intravitreal Injection of Anti-TNF-Alpha Antibodies. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2630.
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Tumor necrosis factor- (TNF-) functions as a proinflammatory cytokine that aggravates uveitis in animal models of uveitis, experimental autoimmune uveoretinitis (EAU). Clinical findings indicated that infliximab, an anti-TNF- chimeric monoclonal antibody, has improved symptoms in inflammatory disorders such as rheumatoid arthritis (RA), Crohn’s disease, and Behcet’s disease. Uveoretinitis as typified by Behcet’s disease, sarcoidosis, and Vogt-Koyanagi-Harada’s disease is one of the major causes of blindness in Asian countries. Anti-TNF- antibody is administrated systemically even when the symptoms are confined to ocular tissues, today. In the present study, anti-TNF- antibody was injected into the vitreous of EAU-susceptible rats, and its efficacy was assessed clinically and histopathologically.
Male Lewis rats were immunized to induce EAU. Peptide R16, sequence 1177-1191 of bovine interphotoreceptor retinoid-binding protein (IRBP) was emulsified in complete Freund’s adjuvant to provide 30µg of peptide in 0.2ml emulsion to each rat. As an additional adjuvant, 1µg of pertussis toxin (PTX) was injected intravenously. Rats received intravitreal injection of 50ng of rabbit anti-mouse TNF- polyclonal antibody into their right eyes by using 30G needles. Clinical severity was observed until day 14 after immunization.
The average clinical severity was 1.05 in the treated eyes and 1.80 in the untreated fellow eyes at day 11 after immunization (p<0.01). The mean clinical score reached 3.30 in untreated eyes, however it remained at 1.45 in antibody-injected eyes at day 14, a peak of the inflammation (p<0.01). No significant differences were observed in eyes between untreated and PBS-injected eyes as controls. Injected antibodies histologically persisted in the vitreous cavity at day 14.
It was shown that intravitreal injection of anti-TNF- antibody was quite effective for rat EAU. The risk of the systemic complications seems to be quite smaller when the product is delivered intravitreally than systemically. Topical administration of anti-TNF- antibodies may be a promising treatment for autoimmune ocular inflammatory diseases.
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