Latent and active plasminogen activator in corneal ulceration

Previous studies of alkali burns have provided evidence for an important role of the plasminogen activator (PA)/plasmin system in corneal ulceration. Current studies have utilized a sensitive, plasminogen-dependent fluorescent assay to demonstrate that PA is present mostly in a latent (trypsin- or plasmin-activatable) form (proactivator) in cultures of rabbit corneal epithelial cells or normal corneas. Cultures of ulcerating corneas demonstrate only active PA early in organ culture, whereas, latent PA levels increase later in culture. Thus, ulceration is correlated with the apparent conversion of latent to active PA. Moreover, profiles of proactivator and latent collagenase and of active PA and active collagenase in vitro, respectively, are similar, suggesting that activator and collagenase are under coordinate control. Cultures of normal epithelial cells and nonulcerating corneas contain PA molecular weight species of 72,000 and 46,000 MW, and ulcer corneas, species of 72,000, 46,000, and 35,000 MW. Double-diffusion analysis indicates that rabbit epithelial cells, fibroblasts, and ulcer corneas produce urokinase (UK)-like PA; and human cornea extracts and tears also contain PA immunoreactive with anti-UK antibodies. The existence of PA in a latent form identifies another level of regulation in the cascades that lead to stromal ulceration.