title: Aldose reductase inhibitor counteracts the enhanced expression of matrix metalloproteinase-10 and improves corneal wound healing in galactose-fed rats.
abstract: OBJECTIVE
  We investigated the effect of an aldose reductase inhibitor (ARI) and the role of matrix metalloproteinase (MMP)-10 on recovery after corneal epithelium removal in a rat diabetic keratopathy model.
  
  
  METHODS
  Three-week-old Sprague-Dawley rats were fed the following diets for 6 weeks: normal MF chow (MF), 50% galactose (Gal), and 50% Gal containing 0.01% ARI (Gal +ARI). The corneal epithelium was removed using n-heptanol, and the area of epithelial defects was photographed and measured every 24 h. Real-time reverse transcriptase PCR, western blotting, and immunohistochemistry were used to determine the expression profile of MMP-10 and integrin α3.
  
  
  RESULTS
  Compared to the MF control group, the amount of galactitol in the Gal group increased approximately 200-fold, which was reduced to sevenfold by ARI treatment. The area of corneal erosion in the Gal group was significantly larger than in the MF group at 72 h and thereafter (p<0.01, unpaired t test). The expression level of MMP-10 was enhanced at both the protein and mRNA levels by exposure to a high concentration of Gal, while integrin α3 expression decreased at the protein level but remained unchanged at the mRNA level. Delayed epithelial wound healing and alterations in the expression levels of MMP-10 and integrin α3 were normalized by ARI. The corneal erosion closure rate was significantly decreased with topical recombinant MMP-10.
  
  
  CONCLUSIONS
  These studies confirm that the increased expression of MMP-10 induced by Gal feeding is counteracted by ARI treatment and suggest a role of MMP-10 in modulating corneal epithelial wound healing.
authors: Department of Ophthalmology, Faculty of Medical Sciences, University of Fukui, Eiheiji-cho, Yoshida-gun, Fukui, Japan.
authors: Yoshihiro
authors: Y
authors: Takamura
authors: Takafumi
authors: T
authors: Matsumoto
authors: Takeshi
authors: T
authors: Tomomatsu
authors: Takehiro
authors: T
authors: Matsumura
authors: Yuji
authors: Y
authors: Takihara
authors: Masaru
authors: M
authors: Inatani
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003317:Corneal Dystrophies, Hereditary / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D004032:Diet; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000201:enzymology / Q000293:injuries / Q000473:pathology; D004376:Galactitol / Q000378:metabolism; D005690:Galactose / Q000008:administration & dosage* / Q000378:metabolism; D005786:Gene Expression Regulation; D039422:Integrin alpha3 / Q000235:genetics / Q000378:metabolism; D008297:Male; D053506:Matrix Metalloproteinase 10 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014945:Wound Healing / Q000187:drug effects* / Q000235:genetics
chemical_list: D004791:Enzyme Inhibitors; D039422:Integrin alpha3; D004376:Galactitol; D000449:Aldehyde Reductase; D053506:Matrix Metalloproteinase 10; D005690:Galactose