Effects of a new dexamethasone-delivery system (Surodex) on experimental intraocular inflammation models

Graefes Arch Clin Exp Ophthalmol. 2003 Nov;241(11):927-33. doi: 10.1007/s00417-003-0753-2. Epub 2003 Sep 4.

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.

MeSH terms

  • Animals
  • Anterior Chamber / pathology
  • Anti-Inflammatory Agents / administration & dosage*
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / pathology*
  • Cell Count
  • Cytokines / metabolism
  • Dexamethasone / administration & dosage*
  • Drug Delivery Systems
  • Endotoxins
  • Eye / metabolism
  • Eye Proteins / metabolism
  • Male
  • Peroxidase / metabolism
  • Rats
  • Rats, Inbred Lew
  • Retinitis / metabolism
  • Retinitis / pathology*
  • Uveitis / chemically induced
  • Uveitis / metabolism
  • Uveitis / pathology*

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Endotoxins
  • Eye Proteins
  • endotoxin, Escherichia coli
  • Dexamethasone
  • Peroxidase