EVIDENCE FOR A ROLE OF THE PLASMINOGEN ACTIVATOR-PLASMIN SYSTEM IN CORNEAL ULCERATION

  • 1 January 1980
    • journal article
    • research article
    • Vol. 19  (10) , 1204-1221
Abstract
Plasminogen is present in the cornea and is activated to plasmin by a plasminogen activator. Plasmin activates latent collagenase. This system could initiate and perpetuate the collagen degradation of corneal ulceration. This system in the cornea was investigated. Plasmin activated latent collagenase from organ cultures of ulcerating rabbit corneas and from fibroblast cultures derived from such corneas. Similar to activation by trypsin and activation by plasmin resulted in the conversion of the 40,000 MW latent form to an active species of 23,000 MW. Explants of normal or alkali-burned, ulcerating corneas demonstrated plasminogen-dependent lysis of fibrin clots; frozen sections of these corneas demonstrated that lysis began in the superficial stroma near the periphery of the cornea. Multiple freeze-thawed ulcerating corneas, but not normal corneas, showed initial lysis, not peripherally but at the ulcer region containing polymorphonuclear leukocytes. The fact that the peripheral lytic pattern existed in corneas obtained from eyes prefrozen in liquid N before excision of the corneas implied that plasminogen activator was normally contained in cells in vivo and was not made only in response to tissue injury. There was no correlation between the location of blood vessels or the presence of the corneal endothelium and the plasminogen-dependent lysis. Plasminogen activator from the ulcerating cornea and from fibroblasts was characterized by sodium dodecyl sulfate-gel electrophoresis of its cleavage products of plasminogen. The activator cleaved plasminogen into H- and L-chain fragments similar to those produced from plasminogen by urokinase. Plasminogen activator activity was quantitated by a new assay that restricts diffusion of the enzyme to 1 dimension into a narrow bore tube. The daily addition of plasminogen to cultures of ulcerating corneas resulted in earlier rises of plasminogen activator, collagenase and collagen degradation fragments in the culture media. Although total plasminogen activator levels were not increased by the addition of plasminogen to culture, levels of collagenase and solubilized collagen were approximately doubled. The plasminogen activator-plasmin system may play an important role in the destruction of the stromal matrix in corneal ulceration.

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