Plasminogen activator in human tears

Abstract

SUMMARYMeasurements were made of the nature and levels of pi as minogen activator in human tears using, as a model of inflammation, patients undergoing cataract surgery. Tis sue plasminogen activator (t-PA) but not urokinase plas minogen activator (u-PA) was found in tears. A wide variation in the range of t-PA in pre-operative tears was found. In those patients not receiving per-operative sub conjunctival betamethasone a significant rise in t-PA was found in tears on the first post-operative day over pre operative levels. A significant fall was noted in those receiving per-operative subconjunctival betamethasone.Plasmin is a potent protease involved in fibrinolysis and in situations of tissue remodelling and neoplasia. It is formed by the action of plasminogen activator (PA) on plas minogen (PIg), an abundant plasma protein.! There are two major endogenous PAs: tissue plasminogen activator (t-PA) of relative molecular mass about 68 000 (Mr 68k), and urokinase (u-PA) of Mr 54k and 34k in its higher and lower molecular weight forms (HMW and LMW) respectively. PA-Plasmin SystemTissue plasminogen activator (t-PA) is essential to vas cular fibrinolysis. It binds to fibrin which stimulates its plasminogen activating activity and it is produced and released by vascular endothelial cells? Urokinase (UK or u-PA) does not bind to fibrin and is concerned with tissue remodelling and cell migration. It is synthesised as a single chain inactive proenzyme, pro-urokinase (pro-UK), by a variety of cells including epitheliaV fibroblastic and inflammatory cells. Many cells bind pro-UK and HMW-UK without loss of PA activity and with relative protection from the action of PA inhibitors. Although binding of u-PA to fibrin does not occur, fibrin will stimu late u-PA induced thrombolysis. PA-Plasmin InhibitorsThe action of plasmin is controlled by naturally occurring Eye (1992) 6,[653][654][655][656][657][658] inhibitors; these include a2-antiplasmin a specific plas min inhibitor, a2-macroglobulin, a non-specific inhibitor of plasmin, and a series of specific inhibitors of plas minogen activators such as plasminogen activator inhibi tor-I and -2 (PAI-I and PAI-2) and protease nexin, a cell surface inhibitor, which have differing affinities for t-PA and u-PA (e.g. PAI-I is a more potent inhibitor of t-PA than u-PA whereas PAI-2 is more effective against u-PA). PAI-l and PAI-2 have little effect on plasmin activity.! Ti ssue DistributionImmunoreactive t-PA is widely distributed in ocular tis sues, including the corneal endothelium and epithelium, the conjunctiva, the trabecular meshwork, lens epithe lium, peripheral vitreous, inner retina, and all vascular endothelia.4 The concentration in human aqueous humour is low,5.6 while it is present both in the tears and in the lac rimal fluid.Roles proposed for ocular PA have included remodell ing (lens epithelium), regulation of the resistance to aque ous outflow (trabecular meshwork) and maintenance of canalicular patency (tears). The potential therapeutic value of fibrinolytic agents has bee...

The role of hepatocyte growth factor in corneal wound healing

“…The activation process in avascular tissues such as the cornea is less well understood and remains understudied. Amongst these proteases, u-PA and t-PA are known to be present in the cornea and t-PA is found in tears (Geanon et al , 1987; Stevens et al , 1992; Watanabe et al , 2003; Warejcka et al , 2011). These proteases represent the most likely candidates to activate HGF through enzymatic processing (Mars et al , 1993).…”