Distribution of Tissue Plasminogen Activator in Human and Monkey Eyes

Tripathi, Brenda J.; Geanon, John D.; Tripathi, Ramesh C.

doi:10.1016/s0161-6420(87)33278-6

Cited by 51 publications

(28 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the central nervous system (CNS) tPA plays a role in neuronal plasticity (34,35) and neuronal regeneration (36)(37)(38), whereas uPA plays a role in astrocyte proliferation and tissue remodeling (39,40). A number of previous studies have demonstrated the presence of tPA and uPA in various eye tissues including, retinal neovascular membranes (41,42), and in normal (43)(44)(45)(46) and diabetic retinas (47). In a clinical setting, tPA has been used to treat stroke patients (48,49), as well as patients with submacular hemorrhage (50)(51)(52)(53)(54).…”

Section: Introductionmentioning

confidence: 99%

Plasminogen activators promote excitotoxicity‐induced retinal damage

2005

View full text Add to dashboard Cite

Increased levels of extracellular L-glutamate have been suggested to play a role in retinal damage in a number of blinding diseases such as glaucoma and diabetic retinopathy. Although glutamate can cause retinal damage, in part, by hyper-stimulating its receptors ("excitotoxicity"), the down-stream events that lead to retinal damage are poorly understood. In this study, we injected kainic acid (KA), a glutamate receptor agonist that specifically hyper-stimulates non-NMDA-type receptors, into the vitreous humor of CD-1 mice and have investigated the role of plasminogen activators (PAs) [tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA)] in excitotoxicity-induced retinal damage. Injection of KA into the vitreous humor led to an up-regulation in tPA and an induction in uPA activity in the retina and this was associated with activation of zymogen plasminogen to active plasmin. Immunocytochemical analysis indicated that retinal ganglion cells (RGCs), constitutively, express tPA and release it into the extracellular space upon KA injection. Immunocytochemical analysis also indicated an increase in uPA in the nerve fiber layer after KA injection which was absent in the control retinas. These events were associated with apoptotic death of cells initially in the ganglion cell layer and subsequently in the inner and outer nuclear layer, associated with loss of both RGCs and amacrine cells. These phenomena were inhibited when recombinant plasminogen activator inhibitor (rPAI-1) or tPA-STOP were injected into the vitreous humor with KA, whereas a plasmin inhibitor, alpha-2-antiplasmin, failed to attenuate KA-induced retinal damage. Taken together, these results suggest that inhibition of plasminogen activators might attenuate retinal damage in blinding retinal diseases in which hyper-stimulation of glutamate receptors is implicated as a causative factor to retinal damage.

show abstract

Section: Introductionmentioning

confidence: 99%

Plasminogen activators promote excitotoxicity‐induced retinal damage

2005

View full text Add to dashboard Cite

show abstract

“…The corneal epithelium contains plasmin ogen activators [Lantz and Andersson, 1982;Tripathi et al, 1987] and has been shown to release them during corneal epithelial wound healing [Chan, 1986], leading to activation of the PAPS. Furthermore, PAPS seems to be involved in pathological processes such as corneal ulceration and vascularization [Ber man et al, 1980[Ber man et al, , 1982,…”

Section: Discussionmentioning

confidence: 99%

Plasmin and Epidermal Growth Factor in the Tear Fluid of Contact-Lens Wearers: Effect of Wearing Different Types of Contact Lenses and Association with Clinical Findings

Setten

Tervo²,

Andersson³

et al. 1990

Ophthalmic Res

View full text Add to dashboard Cite

The concentrations of plasmin and epidermal growth factor were determined in tear fluid (TF) samples from wearers of different types of contact lenses (CLs) during and after cessation of CL wear (CLW). TF samples of 50 healthy eyes served as controls. The plasmin concentrations in the control group (0.4 ± 0.1 μg/ml; mean ± SEM) were significantly lower (p < 0.001) than in the group of soft CL (SCL) wearers during CLW (1.2 ± 0.2 μg/ml). Cessation of CLW led to a decrease in TF plasmin concentrations from 1.2 ± 0.2 to 0.6 ± 0.1 μg/ml in the group of SCL wearers (p < 0.001), from 1.5 ± 1.1 to 0.3 ± 0.2 μg/ml in the group of extended-wear SCL wearers (p > 0.05) and from 0.4 ± 0.3 to 0.0 ± 0.0 μg/ml in the group of gas-permeable CL wearers (p > 0.05). After CLW cessation, TF plasmin levels of CL wearers did not differ from those of controls. The occurrence of plasmin in TF was associated with a higher degree of corneal neovascularization and with the presence of limbal injection. The concentrations of epidermal growth factor in TF were not significantly altered by the discontinuation of CLW.

show abstract

“…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.…”

Section: Ti Ssue Distributionmentioning

confidence: 99%

Plasminogen activator in human tears

Stevens

Marshall

Benjamin

et al. 1992

Eye

View full text Add to dashboard Cite

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...

show abstract

Distribution of Tissue Plasminogen Activator in Human and Monkey Eyes

Cited by 51 publications

References 16 publications

Plasminogen activators promote excitotoxicity‐induced retinal damage

Plasminogen activators promote excitotoxicity‐induced retinal damage

Plasmin and Epidermal Growth Factor in the Tear Fluid of Contact-Lens Wearers: Effect of Wearing Different Types of Contact Lenses and Association with Clinical Findings

Plasminogen activator in human tears

Contact Info

Product

Resources

About