Matrix metalloproteinase levels in dog corneas with wounds

Abstract

PURPOSE: To determine matrix metalloproteinase (MMP) 2 and MMP 9 expression in acute and chronic experimentally wounded canine corneas and keratectomy samples from canine patients with spontaneous chronic corneal epithelial defects (SCCEDs). METHODS: Mechanical debridement was performed unilaterally in 25 healthy dogs for the acute wound study. Twenty-four hours (n = 8), 48 hours (n = 5), 72 hours (n = 3), or 1 week (n = 9) after wounding, the dogs were euthanized. Debridement was performed once weekly for 8 weeks for the chronic study (n = 8). Therapeutic superficial keratectomies (n = 16) were performed on SCCED patients. Gelatin zymography and immunohistochemistry were performed. RESULTS: Acute wounds showed upregulation of MMP 9 at all time points. At 7 days after wounding, values diminished markedly but remained elevated above those of unwounded controls. SCCED and chronic wound samples showed a significant increase in MMP 9 compared with controls but were less than that of acute wounds. There was no significant difference between chronic wounds versus SCCED samples. Fellow control eyes showed significant upregulation of MMP 9 in tandem with wounded eyes. There was no significant difference in values for MMP 2 in wounded corneas or SCCED compared with those of controls. Immunhistochemistry localized MMP 9 to predominantly the epithelium with some staining of keratinocytes and stroma. CONCLUSIONS: The dog exhibits similar MMP expression during corneal wound healing to that of other species. The lack of significant difference in MMP expression between SCCED and chronic wounds suggest that MMP 2 and 9 are not involved in the pathophysiology of SCCED and are more likely altered secondary to a chronic epithelial defect.