Cellular changes of phenotype and collagenase‐1 expression in healing corneal stromal cells

Abstract

Matrix metalloproteinases (MMPs) have been implicated in corneal diseases of the eye. Among the MMPs, collagenase‐1 (MMP‐1) participates in remodeling the extracellular matrix of corneal stroma during wound healing. Here the temporal expression patterns of both IL‐1α and collagenase‐1 were examined during regenerative corneal wound healing. IL‐1α was highly expressed in the healing epithelium at 3 d after epithelial abrasion wound, thereafter its expression returned to normal level. Primary cultured quiescent stromal cells (keratocytes) from uninjured normal cornea were round‐shaped and did not expresse collagenase‐1. However, freshly‐cultured stromal cells isolated 3d after epithelial abrasion wound (abrasion wound) underwent marked morphological changes, and a certain percentage of cell populations was transformed into fibroblasts. By immunofluorescence, collagenase‐1 expression was detected only in spindle‐shaped fibroblasts. Interestingly, most freshly‐isolated cells from remodeling corneal repair tissue 10 d after abrasion injury were found to have fibroblastic morphology, and also constitutively expressed a high level of collagenase‐1 in vitro primary culture. However, its expression was not found in the cells isolated 14 d after wound and cells seemed to have returned to normal quiescent stromal cells. Taken together, these results suggest that differentially expressed IL‐1α in the epithelium might play important roles in wound healing, and important signalling pathways are altered as cells take on the fibroblastic morphology.