title: Plasminogen activator (urokinase) causes vascularization of the cornea.
abstract: The presence of a peripheral zone of (presumed intracellular) plasminogen activator in the normal rabbit cornea has suggested that activator, once released, might regulate the permeability of limbal vessels and angiogenesis, by plasmin-dependent pathways. Plasminogen activator (urokinase [UK]) in rabbit serum albumin (RSA) was injected once (20 microliter, 3.7 CTA U) into the corneal stroma, 2 mm from the limbus. Sprouts arose from the engorged circumlimbal vessels (16 of 20 corneas) beginning on the third day and grew into the cornea over the next several days. Histologically, PMNs were observed in association with growing vessels. Contralateral corneas injected with UK (in RSA) previously inactivated by 99.7% with the specific active site inhibitor, Phe-Ala-Arg-chloromethyl ketone showed minimal vessel engorgement or stromal edema and no vascularization (0 to 20 corneas). Injuries to the so-called (plasminogen activator-containing)"critical zone" of the cornea which elicit neovascularization possibly do so by causing extracellular release of endogenous plasminogen activator. Thus, in addition to initiating the destructive events of ulceration, activator might initiate increases in vessel permeability and also neovascularization, which would result in the eventual arrest of ulceration.
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D003315:Cornea / Q000098:blood supply / Q000187:drug effects*; D003320:Corneal Ulcer / Q000503:physiopathology*; D010450:Endopeptidases / Q000494:pharmacology*; D009389:Neovascularization, Pathologic / Q000187:drug effects*; D010960:Plasminogen Activators / Q000494:pharmacology; D011817:Rabbits; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology*
chemical_list: D000590:Amino Acid Chloromethyl Ketones; C033597:phenylalanyl-alanyl-arginine chloromethyl ketone; D010450:Endopeptidases; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator