Purpose: EIU in rat, a model for severe uveitis in human is characterized by an inflammatory cell infiltration mainly in the anterior uvea but also in the retina. Cytokines, particularly IL-6 and TNF and nitric oxide (NO) are locally released during uveitis. Iontophoresis is a non invasive methods to achieve high concentrations of drugs in the ocular media and it has been demonstrated that Dexamethasone (Dexa) can be delivered into the vitreous by transscleral iontophoresis. We investigated the potential of trans-corneo-scleral iontophoresis of Dexa to inhibit EIU, TNF and NO production and TNF and inducible NO synthase (NOS-II) mRNA. Iontophoresis administration of Dexa was compared to intraperitoneal injection. Methods: EIU was induced in Lewis rats by a systemic injection of LPS (150μg) and simultaneously iontophoresis of Dexa was performed We used a custom-made 1ml reservoir-electrode covering the cornea, the limbus, and the first millimeter of the sclera, a free-flow (1mg/ml) Dexa (C22H29 FO9FW 392.5; Sigma) solution, and a constant current power unit were used (4 minutes, 400 μA). Ocular inflammation was evaluated 2 and 16 hrs after LPS injection by slit-lamp examination, inflammatory cell infiltration by counts on histological sections, TNF titration ( L-929 bioassay) in serum, aqueous humor (AH) and vitreous (V), NO formation in AH and V(nitrite release by Griess reaction). mRNA of TNF NOS-II were evaluated by RT-PCR in iris/ciliary body (ICB) and in the retina (R). Results: Iontophoresis of Dexa significantly inhibited at clinical (p < 0.0001) and histological level (p= 0.001), both anterior and posterior uveitis as efficiently as intraperitoneal administration of Dexa. Protein in AH (p= 0.001) and in the V (p=0.008), local production of TNF (p < 0.0001), nitrite (p < 0.001), mRNA of TNF and NOS-11 were significantly reduced in ICB and R by iontophoresis of Dexa. No clinical nor histological tissue damage could result from iontophoresis .Conclusions: Iontophoresis is a non invasive drug delivery system allowing Dexa treatment of both anterior and posterior uveitis without side-effects, with an inhibition of TNF and NOS-II at a transcriptionnal level. It could be an alternative to systemic administration of glucocorticoids in severe ocular inflammation.
|Original language||English (US)|
|Journal||Investigative Ophthalmology and Visual Science|
|State||Published - Feb 15 1996|
ASJC Scopus subject areas
- Sensory Systems
- Cellular and Molecular Neuroscience