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Tissue plasminogen activator synthesis by trabecular cells and its implications for fibrinolytic therapy of the eye
Author(s) -
Tripathi Ramesh C.,
Park James K.,
Tripathi Brenda J.,
Ts'ao Chunghsin
Publication year - 1989
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430180308
Subject(s) - trabecular meshwork , tissue plasminogen activator , fibrinolysis , fibrin , proteases , aqueous humor , chemistry , glaucoma , plasminogen activator , thrombin , medicine , ophthalmology , endocrinology , immunology , biochemistry , platelet , enzyme
Tissue plasminogen activator (t‐PA) has proved to be an effective drug for intravascular fibrinolysis. We have found that the trabecular meshwork system, which regulates the outflow of the aqueous humor in the eye, normally contains a significant amount of t‐PA (0.2 IU/mg protein). When we experimentally introduced 0.2 ml autologous plasma into the anterior chamber of dog eyes, the amount of t‐PA in the trabecular meshwork increased 2.5‐fold within 90 minutes. In cultured porcine trabecular meshwork cells, exposure to 10 U/ml thrombin for 24 hours caused a maximum rise in the concentration (0.82 ng/ml) and in the activity (0.63 IU/ml) of t‐PA. Despite this synthesis of t‐PA by the trabecular meshwork system and other structures of the eye, as well as its normal level in the aqueous humor, a delay in the dissolution of fibrin in the anterior chamber occurs in various clinical conditions, and this compromises the structural and functional integrity of the ocular tissues. Because the locally produced proteases are apparently insufficent to resolve rapidly the fibrin, and based on our present and previous investigations in the eye, we advocate the exogenous administration of t‐PA when rapid fibrinolysis must be behieved. We propose, with caution, a guideline for the therapeutic use of t‐PA in the eye.