Effects of a new dexamethasone-delivery system (Surodex) on experimental intraocular inflammation models.
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.
Kodama
Masuhiro
M
Department of Ophthalmology, University of Tokyo Graduate School of Medicine, Tokyo, Japan. mkodama@gol.com
Numaga
Jiro
J
Yoshida
Atsushi
A
Kaburaki
Toshikatsu
T
Oshika
Tetsuro
T
Fujino
Yujiro
Y
Wu
Guey-Shuang
GS
Rao
Narsing A
NA
Kawashima
Hidetoshi
H
D000818:Animals; D000867:Anterior Chamber / Q000473:pathology; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001327:Autoimmune Diseases / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D004731:Endotoxins; D005123:Eye / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000378:metabolism / Q000473:pathology*; D014605:Uveitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004731:Endotoxins; D005136:Eye Proteins; C044101:endotoxin, Escherichia coli; D003907:Dexamethasone; D009195:Peroxidase