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K. Oh–i, H. Keino, N. Yamakawa, K. Murase, Y. Usui, T. Kezuka, M. Takeuchi, H. Goto, M. Usui; Intravitreal Injection of Tacrolimus (FK506) Suppresses Experimental Autoimmune Uveoretinitis in Rats . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4543.
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The current study was designed to determine whether intravitreal injection of tacrolimus (FK506) suppresses experimental autoimmune uveoretinitis (EAU) in rats.
Normal Lewis rats received intravitreal injection of tacrolimus (10 µg/5µl/mouse). On days 2 and 7, eyes were enucleated and histological examination was performed. Lewis rats were immunized with interphotoreceptor retinoid binding protein (IRBP) peptide (R14) and given intravitreal injection of tacrolimus (5 or 10 µg/5µl/mouse) on day 12 after immunization. Intraocular inflammation was assessed by slit lamp biomicroscopy and histopathological examination. IL–2, IFN–γ, and TNF–α protein levels in the extracts from the eyes of immunized rats were measured by ELISA. To evaluate the systemic effect of intravitreal injection of tacrolimus, delayed hypersensitivity (DH) to IRBP peptide was measured by ear swelling responses.
In tacrolimus–treated eyes of normal rats, no retinal toxicity was detected histologically. In IRBP–immunized rats, clinical scores showed that tacrolimus–treated eyes had significantly less severe inflammation than vehicle–treated eyes. Histopathological examination revealed reduced recruitment of inflammatory cells and limited retinitits in tacrolimus–treated eyes. The amounts of IFN–γ and TNF–α were decreased in tacrolimus–treated eyes. Finally, DH responses to IRBP peptide were not impaired in tacrolimus–treated rats.
Intravitreal injection of tacrolimus was highly effective in suppressing the ongoing process of anterior and posterior ocular inflammation of EAU in rats. This treatment may be useful in the management of patients with severe uveitis.
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