EXPRESSION OF GELATINASE-A AND GELATINASE-B, AND TIMP-1 AND TIMP-2 DURING CORNEAL WOUND-HEALING

PURPOSE. To determine the expression of gelatinases A and B and the lo calization of tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP -2 during the early stages of corneal wound healing in rats. METHODS. One eye each of 30 adult Sprague-Dawley rats was treated with excimer laser keratectomy; the other eye was untreated. Frozen sections of cor neas obtained 6, 18, and 24 hours and 5 and 7 days after wounding were used to perform immunoconfocal microscopy and in situ hybridization. RESULTS. Gelatinase B was immunolocalized to the basement membrane zon e and superficial stroma, and its mRNA was exclusively localized to ba sal epithelial cells migrating across the wound at 18 and 24 hours and 5 days after mounding. Tissue inhibitor of metalloproteinase-1 was al so immunolocalized to the basement membrane zone and superficial strom a at the same time points. Gelatinase A was immunolocalized re the epi thelium and stroma of normal corneas and was predominant in the basal epithelium and superficial stroma at 3 and 7 days after wounding. In s itu hybridization confirmed gelatinase A expression by the epithelial cells and the stromal keratocytes. Tissue inhibitor of metalloproteina se-2 was immunolocalized to the epithelium in normal and wounded corne as. Intense TIMP-2 labeling of the basement membrane zone was noted 3 days after wounding. CONCLUSIONS. Unlike gelatinase A, gelatinase B is expressed exclusively by migrating basal epithelial cells after wound ing. The matrix metalloproteinase-tissue inhibitor of metalloproteinas e (MMP)/TIMP systems map plap an important role in the early stages of corneal wound healing after excimer laser keratectomy.