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J. S. Paula, M. B. Oliveira, F. Chahud, C. M. Modulo, E. M. Rocha, F. Q. Cunha; Effect of Isosorbide Dinitrate on Corneal Hyperalgesia Induced by Lipopolysaccharide in Rats. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2381.
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© ARVO (1962-2015); The Authors (2016-present)
Nitric oxide (NO) is involved in peripheral hyperalgesia control, including the cornea (Paula, JS et al., ARVO, 2006). The aim of this study was to evaluate the effect of isosorbide dinitrate (DNI - a NO donor) on corneal hyperalgesia inhibition in a rat model of superficial keratitis induced by lipopolysaccharide (LPS).
Hyperalgesia was studied in a series of experiments with induction of inflammatory keratitis in the right eye of Wistar rats, by corneal abrasion and double exposure to topical LPS (B4, 50ug in day 1 and 5ug in day 3, for 20 seconds). Following initial exposure to LPS, 15 animals were treated with different concentrations of topical DNI q2h (200ug, 65ug and 20ug), 5 animals were treated with topical prednisolone 1% q2h, and 15 animals were treated with saline. More 5 animals had no exposure to LPS (controls). Behavioral sensitization to chemical stimuli was determined in day 4, by counting the number of blinks in 40 seconds, after one drop of 0.01 µM capsaicin. Histopathological analysis was also performed, with attention to neutrophil infiltration.
Slit-lamp examination revealed white clouding areas in the corneal stroma of keratitis-induced eyes, between day 3 and day 10. Instillation of capsaicin onto the corneal surface of eyes exposed to LPS showed significantly higher mean number of blinks than controls (7.4 ± 1.3 versus 3.0 ± 0.8 blinks; P=0.019). Topical treatment of keratitis-induced eyes with DNI (65ug, q2h) reduced significantly the capsaicin-induced blinks (2.2 ± 0.4 blinks; P=0.011), as well as prednisolone did (2.7 ± 0.4 blinks; P=0.010). Treatment with the different concentrations of DNI had comparatively lower significance. There was no significantly difference of the mean blinks number between DNI treated and control eyes (P=0.659). Eyes exposed to LPS had a significantly higher amount of neutrophil infiltration than controls (P=0.004), however they were not different from DNI treated eyes (P=0.402).
The results indicate that LPS applied after corneal abrasion can induce an experimental inflammatory keratitis, with neutrophil infiltration and hyperalgesia. Moreover, the present findings also suggest that isosorbide dinitrate (65ug/4ul) can reduce corneal hyperalgesia in this experimental keratitis, with no difference in neutrophil migration.
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