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Effects of a new dexamethasone-delivery system (Surodex) on experimental intraocular inflammation models
Authors:Email author" target="_blank">Masuhiro?KodamaEmail author  Jiro?Numaga  Atsushi?Yoshida  Toshikatsu?Kaburaki  Tetsuro?Oshika  Yujiro?Fujino  Guey-Shuang?Wu  Narsing?A?Rao  Hidetoshi?Kawashima
Institution:(1) Department of Ophthalmology, University of Tokyo Graduate School of Medicine, Tokyo, Japan;(2) Doheny Eye Institute, University of Southern California, Los Angeles, CA, USA;(3) Department of Ophthalmology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan;(4) Present address: Department of Ophthalmology, Musashino Red Cross Hospital, 1-26-1 Kyonanchou, Musashino-shi, 180-8610 Tokyo, Japan
Abstract:Background To investigate the effects of a new biodegradable dexamethasone drug delivery system, Surodex, in two experimental intraocular inflammation models; endotoxin-induced uveitis (EIU) and experimental autoimmune uveoretinitis (EAU).Methods Surodex was inserted into the right anterior chambers (ACs) of rats. In the EIU experiment, protein concentration, cell infiltration, and myeloperoxidase (MPO) activity in the aqueous humor were measured 24 h after injection. Eyes were evaluated histopathologically. In the EAU experiment, firstly, Surodex was administered at various days after immunization. Then, Surodex was administered on day 9 and eyes were evaluated histopathologically. Intraocular cytokine levels (IFN-gamma and IL-4) were investigated.Results In the EIU experiments, eyes with Surodex exhibited significantly reduced inflammation compared with contralateral controls. Protein concentrations, cell infiltrations, as well as MPO activity were reduced. In the EAU experiments, all rats with Surodex given on days 0 or 7 showed no or significantly reduced inflammation in both eyes. Rats treated on day 12 developed reduced inflammation only in the treated eyes. IFN-gamma levels were significantly lower in the eyes with Surodex, whereas IL-4 was not detectable.Conclusions This new, biodegradable corticosteroid drug-delivery system is highly effective in suppressing intraocular inflammation, and should be a useful tool to manage uveitis in humans.
Keywords:Endotoxin-induced uveitis  Experimental autoimmune uveoretinitis  Drug delivery system  Crinical score  Histopathological score
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