Reduction of corneal edema in endotoxin-induced uveitis after application of L-NAME as nitric oxide synthase inhibitor in rats by iontophoresis

Francine F. Behar-Cohen, Michelle Savoldelli, Jean Marie Parel, Olivier Goureau, Brigitte Thillaye-Goldenberg, Yves Courtois, Yves Pouliquen, Yvonne De Kozak

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60 Scopus citations

Abstract

PURPOSE. To investigate the involvement of the cornea during endotoxin- induced uveitis (EIU) in the rat and the effect of N(γ)-nitro-L-arginine methyl ester (L-NAME) as nitric oxide synthase (NOS) inhibitor, administered by iontophoresis. METHODS. EIU was induced in Lewis rats that were killed at 8 and 16 hours after lipopolysaccharide (LPS) injection. The severity of uveitis was evaluated clinically at 16 hours, and nitrite levels were evaluated in the aqueous humor at 8 hours. Corneal thickness was measured, 16 hours after LPS injection, on histologic sections using an image analyzer. Transmission electron microscopy (TEM) was used for fine analysis of the cornea. Transcorneoscleral iontophoresis of L-NAME (100 mM) was performed either at LPS injection or at 1 and 2 hours after LPS injection. RESULTS. At 16 hours after LPS injection, mean corneal thickness was 153.7 ± 5.58 μm in the group of rats injected with LPS (n = 8) compared with 126.89 ± 11.11 μm in the saline-injected rats (n = 8) (P < 0.01). TEM showed stromal edema and signs of damage in the endothelial and epithelial layers. In the group of rats treated by three successive iontophoreses of L-NAME (n = 8), corneal thickness was 125.24 ± 10.36 μm compared with 146.76 ± 7.52 μm in the group of rats treated with iontophoresis of saline (n = 8), (P = 0.015). TEM observation showed a reduction of stromal edema and a normal endothelium. Nitrite levels in the aqueous humor were significantly reduced at 8 hours by L-NAME treatment (P = 0.03). No effect on corneal edema was observed after a single iontophoresis of L-NAME at LPS injection (P = 0.19). Iontophoresis of saline by itself induced no change in corneal thickness nor in TEM structure analysis compared with normal rats. CONCLUSIONS. Corneal edema is observed during EIU. This edema is significantly reduced by three successive iontophoreses of L-NAME, which partially inhibited the inflammation. A role of nitric oxide in the corneal endothelium functions may explain the antiedematous effect of L-NAME.

Original languageEnglish (US)
Pages (from-to)897-904
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume39
Issue number6
StatePublished - May 1 1998

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Behar-Cohen, F. F., Savoldelli, M., Parel, J. M., Goureau, O., Thillaye-Goldenberg, B., Courtois, Y., Pouliquen, Y., & De Kozak, Y. (1998). Reduction of corneal edema in endotoxin-induced uveitis after application of L-NAME as nitric oxide synthase inhibitor in rats by iontophoresis. Investigative Ophthalmology and Visual Science, 39(6), 897-904.