IONTOPHORESIS OF DEXAMETHASONE IN THE TREATMENT OF ENDOTOXIN-INDUCED-UVEITIS IN RATS

The purpose of this study was to evaluate the efficacy of a Coulomb Co ntrolled Iontophoresis system (CCI) in the local delivery of corticost eroids for the treatment of uveitis. The therapeutic efficacy of Dexam ethasone (Dex) administered by CCI was compared to systemic injection and to topical application with the iontophoresis apparatus in the abs ence of electrical current. The evaluation was done in the treatment o f the endotoxin-induced uveitis (EIU) model, and in the effect on TNF gene expression in the iris/ciliary body as well as in the retina and on TNF levels in aqueous humor and vitreous. Dex was administered eith er at the time of LPS injection or 5 hours later. For iontophoresis, w e used a 1 ml reservoir-electrode covering the cornea, the limbus, and the first millimeter of the sclera. The applied electrical current wa s of 400 mu A during four minutes with a total surface charge of 0.4 C cm(-2). EIU was evaluated by clinical examination, by counts of intra ocular inflammatory cells on histological sections, and by measuring t he protein levels in the aqueous humor and in the vitreous. The TNF-al pha gene expression in the iris and ciliary body, and in the retina wa s evaluated by RT-PCR. The systemic effect of Dex delivered by CCI was evaluated on the level of serum TNF-alpha in EIU. Our results demonst rated that local administration of Dex by CCI inhibited anterior and p osterior signs of intraocular inflammation as effectively as systemic administration, with no effect on systemic level of TNF. In the anteri or and posterior segments of the eye, the protein exudation, TNF level s and the cellular infiltration were inhibited. The TNF-alpha gene exp ression was inhibited in the anterior as well as the posterior segment of the eye. No clinical nor histological damage were caused by the CC I apparatus. In conclusion, CCI administration of Dex allows for a the rapeutic effect on the posterior as well as the anterior segment of th e eye, and may present a viable alternative to systemic administration of glucocorticoids in severe ocular inflammations. (C) 1997 Academic Press Limited.