Inrtravitreal Injection of Tacrolimus( FK506) Suppresses Experimental Uveitis without Damaging the Retina in Rabbit

Abstract

Abstract: : Purpose: Although FK506 has been demonstrated to be an immunosuppressive agent, long standing systemic administration of FK506 produces adverse side effects in the liver and kidney. Recently, FK506 has been shown to possesses neuroprotective actions on the retinal ganglion cells in several animal models of retinal ishemia or optic nerve crash. In this study, we examined whether intravitreal injection of FK506 inhibits ocular inflammations, and whether FK506 exhibits neuroprotective effects on the retina in a rabbit model of experimental uveitis (EU). Methods: EU was induced in Japanese white rabbits by intravitreal administration of 50 µ g/ m l of bovine serum albumin (BSA), on day 14 after systemic immunization with BSA emulsificated in complete Freunds adjuvant (CFA). On day 1 after BSA intravitreal injection, FK506 was injected at concentrations of 20-40 µg/50 µ l into the vitreous of unilateral eye, after paracentasis. Contralateral eyes received betamethasone or balanced salt solution. The rabbits were examined on days 1, 3, 7, 14 and 30 days after intravitreal injection of drug, by slit-lamp microscopy, funduscopy, and electroretinogram. The rabbits were sacrified at the test days and their eyes were enucleated and ocular manifestations were examined histologically. Result: Intraocular inflammation was significantly reduced in rabbits given intravitreous injection of FK506 in clinical and histopathological findings, although TUNEL assay indicated no differences between rabbits treated with and without FK506. In addition, amplitudes of a- and b-waves of ERG were restored in FK506 –treated eyes. Conclusion: Intravitreal injection of FK506 inhibited ocular inflammation in a rabbit model of EU without damaging the retina, suggesting a possibility of treating human uveitis without systemic side effects.

Keywords: uveitis-clinical/animal model • vitreous • pharmacology