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Yoshihiro Takamura, Takahumi Matsumoto, Takeshi Tomomatsu, Takehiro Matsumura, Masaru Inatani; The Effect Of Aldose Reductase Inhibitor During Corneal Wound Healing And The Expression Of MMP-10 In Rat Diabetic Keratopathy. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3549.
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© ARVO (1962-2015); The Authors (2016-present)
To estimate the effect of aldose reductase inhibitor (ARI; ranirestat) during the recovery from the removal of corneal epithelium in rat diabetic keratopathy model and investigate the role of matrix metaloproteinases (MMP)-10, a potent inhibitor of epithelial adhesion.
Three-weeks old SD (Sprague-Dawley) rats were separated to the 3 groups according to the diets fed for 6 weeks: normal MF chow (MF), 50% galactose (Gal) and 50% galactose containing 0.01% ARI (Gal +ARI). Accumulated galactitol in the whole of corneal tissue was measured using LC/MS/MS assays. Western blot and immunohistochemistry were examined to investigate the expression-levels of MMP-10 protein. The total corneal epithelium was removed using n-heptanol (Sigma) and the area of epithelial defects was photographed and measured every 24 hrs.
The amount of galactitol in the corneal tissue of Gal group increased to approximately 30-folds in the comparison to the controls (MF), and that was reduced to 7-folds by ARI treatment. The area of corneal erosion in Gal group was significantly larger than MF group at 72 hrs and thereafter, and that of Gal + ARI group was smaller than that of Gal group at 96 hrs and thereafter (p < 0.01, unpaired t-test). MMP-10 was strongly expressed in corneal epithelium of galactose-fed rats, and the intense of staining was reduced by ARI administration. The results of Western blot showed that the levels of MMP-10 expression were enhanced by galactose feeding, and that was inhibited by ARI treatment.
Galactose-induced galactitol accumulation in the cornea and the deteriorated corneal epithelial wound healing were counteracted by ARI, probably through the modulation of MMP-10 expression.
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