Tissue Plasminogen Activator in Human Aqueous Humor and Its Possible Therapeutic Significance

Tripathi, Ramesh C.; Park, James K.; Tripathi, Brenda J.; Millard, Charles B.

doi:10.1016/0002-9394(88)90707-6

Cited by 45 publications

(17 citation statements)

References 15 publications

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“…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

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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.

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Section: Introductionmentioning

confidence: 99%

Plasminogen activators promote excitotoxicity‐induced retinal damage

2005

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“…tPA is expressed and secreted by various organ systems including the TM (Park et al, 1987; Shuman et al, 1988), and is found in the aqueous humor (Tripathi et al, 1988), suggesting that tPA could have an important role in regulating ECM composition in the TM. Glucocorticosteroids increase the accumulation of ECM components in the TM and decrease outflow facility, and have been shown to elicit reductions in tPA activity in TM organ and cell cultures (Seftor et al, 1994), suggesting a link between these phenomena.…”

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confidence: 99%

Tissue plasminogen activator reduces the elevated intraocular pressure induced by prednisolone in sheep

Candia

Gerometta

Danias

2014

Experimental Eye Research

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“…16 rectly into the anterior chamber. 30 Since 1992, rtPA Some epidemiologic and medical conditions indosages of 6 to 25 g have been used to treat fibrin crease the risk for postoperative inflammation in some reaction after cataract surgery, 7-12 even in children. 10 patients.…”

Section: Resultsmentioning

confidence: 99%