Plasminogen activator activity in vitamin A-deficient rat corneas

Plasminogen activator (PA) activity during epithelial wound healing in vitamin A-deficient rats was investigated to determine whether a relationship exists between corneal defect formation and PA activity. Uniform, central 3 mm diameter corneal epithelial wounds were made by scalpel debridement in vitamin A-deficient and in pair-fed control rats. Cryostat sections of such corneas, taken at various times post-scrape, were overlaid with fibrin films containing plasminogen to examine the distribution of PA activity; and antibodies to tissue plasminogen activator (tPA) or to urokinase-like activator (uPA) were incorporated into the films so that the immunochemical natures of detected PA activities could be determined. Corneas from pair-fed controls showed tPA-dependent lysis in association with the regenerating epithelium as well as in the defect region during epithelial wound healing. Corneas from vitamin A-deficient rats also demonstrated tPA activity in association with corneal epithelium post-scrape but showed no detectable tPA activity in the defect region. Histological examination of the vitamin A-deficient corneas demonstrated that a pseudomembrane composed of PMNs, cell debris, and fibrinous exudate had formed on the scrape-debrided stromal surface. The migrating edge of regenerating epithelium overlaid this membrane and was, therefore, not in contact with the stromal surface. The formation of the pseudomembrane, which delays reepithelialization, might have resulted from the absence of PA activity in the defect region. Both excessive and inadequate levels of PA activity may result in impaired epithelial wound healing.