Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the anterior segment of the eye, fibrin clots must be rapidly resorbed to prevent further fibrosis and scarring. The aqueous humor of patients undergoing cataract surgery was analyzed for the presence of components of the fibrinolytic cascade. In 30 patients, aqueous humor and plasma were compared for their content of urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), plasminogen activators inhibitors (PAIs), plasminogen, and total proteins. With gel electrophoresis and zymographic assays of serial dilutions of plasma and aqueous humor, all these components were found to be present at lower concentrations in aqueous humor than in plasma. For total proteins, the aqueous/plasma ratio was approximately 0.003, and for plasminogen it was 0.001. Interestingly, the aqueous/plasma ratio for uPA was not as low and varied from 0.01 to 0.03. A significant proportion of the uPA in aqueous humor was present in the two-chain active form. In addition to uPA, aqueous humor contained lower levels of tPA, but no detectable levels of reactive plasminogen activators inhibitors (PAIs). The presence of a relatively high concentration of active uPA shows that the proteolytic balance of the aqueous humor in the anterior chamber of the eye is shifted toward fibrinolysis.
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PMID:Urokinase-type plasminogen activator in human aqueous humor. 163 15

We studied the quantitative fluctuations of tissue plasminogen activator (t-PA) activity and antigen in aqueous humor before and after extracapsular cataract extraction and poly(methyl methacrylate) posterior chamber lens implantation. The t-PA activity level was measured by solid phase bioimmunoassay using monoclonal antibody against an epitope apart from the active site of t-PA, and the antigen by ELISA. In our patients the mean preoperative level of t-PA activity was 0.0664 +/- 0.0472 IU/ml (mean +/- SD) and of the antigen, 0.175 +/- 0.024 ng/ml. The t-PA activity level in aqueous humor was markedly decreased on the first postoperative day (0.0042 +/- 0.0037 IU/ml), recovered on the second day (0.0403 +/- 0.0251 IU/ml), and then progressively decreased from the fourth to the seventh days. The t-PA antigen level in aqueous humor increased on the first (0.366 +/- 0.108 ng/ml) and second (0.403 +/- 0.251 ng/ml) postoperative days and gradually decreased from the fourth to seventh days. Under the intracameral condition of the fibrinolytic system, various factors, e.g., serious inflammation or events affecting the balance of coagulation and fibrinolysis, may induce the decrease or depletion of t-PA activity, followed by the pupillary fibrin membrane formation. We suggest that fluctuations of t-PA activity in aqueous humor may affect fibrinous membrane formation over the IOL surface.
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PMID:Postoperative fluctuations of tissue plasminogen activator (t-PA) in aqueous humor of pseudophakes. 194 85

Levels of plasminogen activator (PA), plasminogen (Plg), and antiplasmin activity (APli) were compared in feline aqueous humor obtained from normal eyes, eyes inflamed by chronic mycobacterial-induced uveitis (CMIU), opposite eyes, and in plasma. Fibrin-agar plate microassays were utilized to visually confirm the extent of differences in in vitro fibrinolysis, per se. Chromogenic peptide (S2251) microassays were utilized to quantify differences. Normal AH showed much more available PA than did plasma. However, when APli activity was first neutralized their levels of total PA were comparable. Available PA activity in both normal and CMIU AH was considerably amplified in the presence of trace amounts of free plasmin. Plasma failed to show this response. AH levels of circulating Plg and APli in normal eyes were far below plasma levels. During CMIU, total PA levels remained approximately normal while levels of Plg and APli were greatly increased. The net effect of these concurrent rises was that antiplasmin activity (APli) prevailed over free plasmin formation; i.e., in vitro fibrinolysis was suppressed. Plasma levels of PA, Plg and APli did not change during CMIU. Changes in the normal PA+Plg/APli balance induced by CMIU suggested a hypothetical model of AH fibrinolysis wherein exclusion of APli from the normal anterior chamber and the high levels attained during CMUI are posited as key determinants of AH fibrinolytic capability.
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PMID:Regulation of anterior chamber fibrinolysis. 241 Jan 95

The types, activities and concentrations of plasminogen activator (PA) were examined in the bovine vitreous body and aqueous humor. Molecular weights of PA in the vitreous body and aqueous humor were approximately 66 and 110 kilodaltons (kDa), respectively, as determined by fibrinolysis enzymography. These PA activities were neutralized by anti-human tissue PA (t-PA) IgG but not by anti-human urokinase PA (u-PA) IgG. Both findings indicated that the main PA in the vitreous body and aqueous humor is t-PA. The existence of u-PA could not be confirmed in intraocular fluids. Fibrinolytic activities measured by amidolytic assay were 0.12 +/- 0.01 IU/ml in the vitreous body and 0.04 +/- 0.02 IU/ml in the aqueous humor. High concentrations but relatively low fibrinolytic activities suggested that PA and PA inhibitor coexisted in the intraocular fluids. Moreover, unbound PA inhibitor was not detected by reverse fibrinolysis enzymography. The present study suggests that most of the PA inhibitor combines with PA and forms a complex. PA predominates over PA inhibitor in the intraocular fluids, whereas PA inhibitor predominates in the plasma. The results by Todd's fibrinolysis autography and immunohistochemical staining showed that t-PA was present in the corneal endothelial cells, which are in direct contact with the aqueous humor. This suggests that not only the vascular system but the corneal endothelial cells as well might be a source of the PA of the aqueous humor and possibly of the vitreous body also.
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PMID:Fibrinolytic activity and localization of plasminogen activator in bovine vitreous body and aqueous humor. 249 26

Fibrinolytic activity of aqueous humor was tested by the Astrup fibrin plate lysis technique in 7 patients who had chronic simple glaucoma and was compared with a control group of 7 patients with senile cataract. The plasminogen activator content of aqueous humour in glaucoma patients was remarkably reduced; it was not demonstrable in as many as six out of seven patients. The lysis zones in the control group ranged from 110 to 900 mm2 with an average of 423 mm2. The want of aqueous fibrinolytic activity may have a pathogenetic implication for glaucoma since deposition of fibrin in the angle of the eye to depressed fibrinolytic activity could increase resistance to aqueous flow.
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PMID:Reduced fibrinolytic activity in aqueous humor of chronic simple glaucoma. 653 99

Purified homologous fibrinogen (2.4-9.4 mg) was injected intracamerally in cat eyes at approximate six months intervals for up to 30 months in order to assess, in vivo, the long-term impact of chronic uveitis on anterior segment fibrinolytic capability. Normal and acutely inflamed eyes responded with slow clotting, small clot formation and rapid lysis (2-3 days). Chronically inflamed eyes showed rapid clotting, larger clots and much slower lysis, with BCG-induced uveitis much slower than endotoxin-induced uveitis. Suppression of plasminogen activator levels within aqueous humor of chronically inflamed eyes was indicated, using modified fibrin plate methods. The normal balance between fibrinolysis and fibrinogenesis within tissues bounding the anterior chamber is apparently tilted in favor of the latter function when inflammation is prolonged.
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PMID:Evidence of impaired anterior segment fibrinolytic activity in chronic uveitis. 675 98

Tissue-type plasminogen activator (t-PA), a serine protease that catalyzes the conversion from plasminogen to plasmin, plays an important role in the fibrinolytic system and has also in recent years attracted attention in the field of ophthalmology. In order to examine the role of t-PA in the physiology of the anterior segment, we detected t-PA in aqueous humor by using immunoassays. The samples were taken by keratocentesis prior to cataract or glaucoma surgery. The sample volumes ranged from 50-200 microliters. The quantities of t-PA Ag and plasminogen-activator inhibitor (PAI) Ag were determined by using enzyme-linked immunosorbent assays. We determined t-PA and PAI in the aqueous humor of 54 patients between 32 and 87 years of age. The t-PA Ag levels ranged from 0.2 to 1.9 ng/ml (average 0.8 ng/ml), PAI-Ag from 0.2 to 1.7 ng/ml (average 0.9 ng/ml). The values measured in men were slightly higher than those measured in women. No association between t-PA and PAI levels and accompanying diseases or metabolic disorders was noted. Precise knowledge about the presence of t-PA in aqueous humor is a prerequisite for the recognition of pathological events following intraocular fibrin formation and may be an important basis for the therapeutic use of rt-PA in the intraocular inflammatory process.
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PMID:[Plasminogen activator and PAI. Detection in aqueous humor of the human eye]. 844 55

The uveal layer is thought to hold the largest stores of tissue plasminogen activator (t-PA) within the eye. However, the uveal cell types that contain and could release t-PA to contiguous tissues and fluids have not been clearly identified. In the present study the general distribution pattern of t-PA antigen in fresh rat iris and choroid tissue was determined by immunofluorescence in preliminary light microscopic (LM) cryosections. Transmission electron microscopic (TEM) immunogold localization was then used to detect specific cellular and subcellular sites of t-PA antigen. The primary antibody was rabbit anti-mouse t-PA IgG. The immunofluorescence in preliminary LM cryosections of both tissues was most intense over discrete linear and cross-sectioned structures that resembled the contours of axon bundles. This impression was strengthened when silver impregnation highlighted similar structures in separate sections of the same tissue samples. TEM immunogold labeling of thin sections then confirmed that the t-PA antigen was confined to the axoplasm of both myelinated and unmyelinated perivascular nerve fibers in both the iris and choroid. Gold particles were not observed over axonal membranes, myelin sheaths, Schwann cells, retinal pigment epithelium or vascular endothelial cells. Ultrathin TEM cryosections of the iris showed a localization of some particles over structures that resembled tubules and vesicles within the axoplasm, but not over mitochondria. The axonal location of t-PA was shown by the co-localization of t-PA with an antibody against rat neurofilaments. The typical axon morphology that enclosed the t-PA particle markers in all TEM sections also indicated an axonal location. Separate TEM sections were processed with conventional fixatives and stains to highlight the typical uveal axon morphology, which also confirmed the identity of perivascular axons as the sites of t-PA localization. Affinity of the primary antibody for rat t-PA was shown by an inhibition ELISA against rat uveal tissue extracts and by the inhibition of t-PA activity in aqueous humor. An amidolytic assay was used to quantify t-PA activity. Possible explanations for the preferential immunolocalization of t-PA antigen to the axoplasm of uveal nerve terminals and the need for additional functional studies to confirm a putative neural t-PA synthesis are discussed.
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PMID:Morphologic evidence for a preferential storage of tissue plasminogen activator (t-PA) in perivascular axons of the rat uvea. 923 71

Ocular implants containing fluorometholone (FLM) were prepared using blends of poly (DL-lactic acid) (PLA) and polyvinyl pyrrolidone (PVP). The effect of the fraction of PVP content on the release of FLM from the implant was investigated in vitro. The drug was released from the device by approximately following first order kinetics within the period of 40 d. The release rate gradually increased with an increase in the PVP content. The in vivo study after implantation in the anterior chamber of rabbit eyes indicated that the PLA-PVP implant showed a good correlation between the in vitro and in vivo release of FLM. The present polymer blend implant demonstrated a constant level of FLM in the aqueous humor for one month.
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PMID:Polymer blend implant for ocular delivery of fluorometholone. 947 72

We evaluated the release behavior of FITC-dextran with an average molecular weight of 4,400(FD4), as a model peptide drug, from poly(DL-lactic acid) (PLA) implant. The drug level in the vitreous and its peripheral tissues were measured following the implantation in the rabbit vitreous. The release profile of FD4 from the PLA implant was biphasic; a fraction of the drug molecules incorporated in the polymer implant was swiftly released; then slowly or even negligibly for a certain period of time and finally complete bursting release probably due to bulk erosion of the polymer. The time-course of drug concentration in the vitreous and aqueous humor after implantation showed a constant level for 14 days and then parabola, where the highest concentration appeared around 28 days. The drug concentrations in the retina/ choroid was maintained a constant level for 28 days. After an injection of FD4 in the rabbit vitreous, the drug concentration in those tissues approximately decreased mono-exponentially. These findings suggest that the present implant could be a useful carrier for delivery of macromolecular drugs to the vitreous and its peripheral tissues.
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PMID:[Delivery of macromolecular drugs to the vitreous and its peripheral tissues]. 954 47


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