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Query: UMLS:C0595921 (intraocular pressure)
 11,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some prostaglandins, topically applied, are known to lower intraocular pressure; a few have been shown to increase facility of outflow. Iloprost (ZK36374), a stable PGI2 analog, was tested in rabbits for effect on intraocular pressure and facility, but was found totally inactive on either.
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PMID:The effect of iloprost on the rabbit eye. 245 76

Pathways of arachidonic acid metabolism were identified in freshly prepared and in cultured bovine corneal endothelial cells. The principal pathway of arachidonic acid metabolism in the bovine corneal endothelial cells appears to be the cyclooxygenase pathway with the resultant synthesis of PGI2, PGF2 alpha and PGE2. At least two of these products, PGI2 and PGF2 alpha, are formed by the enzymatic conversion of the substrate, PGH2. Measurements of endogenous prostaglandin production by radioimmunoassay demonstrated that PGE2 was the major arachidonic acid metabolite released, with smaller amounts of PGF2 alpha and the stable hydrolysis product of PGI2, 6-keto PGF1 alpha. The release of all three prostanoids was significantly increased by the addition of the calcium ionophore (A23187), human thrombin, bradykinin and histamine. Basal and stimulated release of prostaglandins by the corneal endothelium may contribute to the regulation of intraocular pressure and also in the modulation of the corneal response to injury.
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PMID:Arachidonic acid metabolism by cultured bovine corneal endothelial cells. 249 58

The effects of prostacyclin (PGI2) upon intraocular pressure and pupil size were examined in anaesthetized rabbits. Intracamerally applied PGI2 within the dosage range of 0.1 to 1.0/microgram led to an increase of the intraocular pressure (IOP) measured directly and continuously, and to a miosis. 6-oxo-PGF1 alpha, the product of hydrolysis of prostacyclin did not influence IOP or reaction of the pupil. Topical single doses of PGI2 of 4 to 80/micrograms on conjunctiva and cornea of the eye had no effect.
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PMID:Intracamerally applied prostacyclin raises the intraocular pressure in the rabbit. 392 98

We have extended our previous observations on the effect of tranylcypromine (TCP) on intraocular pressure (IOP), following topical administration of catecholamines is normal and chemically denervated rabbit eyes. In normal eyes, TCP inhibits the hypotensive phase after topical norepinephrine (nE); less after epinephrine (E); and not at all after isoproterenol. In denervated eyes, the inhibitory effect of TCP on the hypotensive phase of nE and E is enhanced. Phenoxybenzamine (PBA), but not timolol maleate or indomethacin, blocks the effect of TCP on alpha-adrenergic induced hypotension. Prostacyclin-like activity was estimated by bioassay using ADP induced rat platelet aggregation. This activity is significantly reduced in the primary aqueous and in the iris after TCP but it is significantly increased in pooled data of aqueous samples after topical nE. We conclude that the inhibitory effect of TCP on the hypotensive phase after topical E and nE is the result of inhibition of prostacyclin synthesis and not of MAO inhibition nor blockade of alpha-receptors. It is possible that the normal production of prostacyclin by the iris and ciliary body maintains (lower) basal levels of IOP.
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PMID:Does prostacyclin mediate alpha-adrenergic induced hypotension? 675 47

The effect of exogenous prostacyclin (PGI2) on the rabbit eye was investigated. During intravenous infusion, intraocular pressure readings and changes of the luminal diameters of choroidal veins were recorded simultaneously. 5 ng/kg/min induced a reduction of intraocular pressure and no blood flow changes. 25 ng/kg/min resulted in a considerable vasodilatation in the posterior uvea paralleled by an increase in intraocular pressure. These results suggest the explanation that exogenous prostacyclin in high doses causes an augmentation of posterior uveal blood flow and thereby a rise in intraocular pressure. Low (2.5 mg/kg BW) or high (17.5 mg/kg BW) aspirin caused no changes in intraocular pressure, indicating a minor role of endogenous prostaglandins in regulating intraocular tension.
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PMID:Biphasic action of prostacyclin on intraocular pressure. 704 Oct 34

We investigated the effects of prostaglandins (PG) E2, PGD2, PGI2, and its metabolites 6-keto-PGE1 and 6-keto-PGF1 alpha, and U46619 (stable analogue of the PG endoperoxide, PGH2) administered either intravitreally or topically on intraocular pressure (IOP), pupil diameter, aqueous protein, and the entry of polymorphonuclear cells (PMNs) in the aqueous. PGE2, 6-keto-PGE1, U46619, and PGI2 increased IOP after either intravitreal or topical administration in a dose-dependent manner, 6-keto-PGE1 was the most potent in increasing IOP. U46619 and PGI2 increased IOP when administered intravitreally; however, these agents also increased IOP of the contralateral control eye. High doses of 6-keto-PGE1 and PGI2 but not 6-keto-PGF1 alpha or PGE2 increased the IOP of both experimental and contralateral eyes, suggesting that this effect may be due to the entry of these agents into the systemic or intraorbital circulation or to stimulation of neuronal pathways. Intravitreal administration of 6-keto-PGE1, PGE2, and PGI2 increased protein of the aqueous, with 6-keto-PGE1 significantly more potent than other PGs. Topically applied PGE2 and 6-keto-PGE1 also increased protein content of the aqueous at doses that elevated IOP. However, topical 6-keto-PGE1 alpha at doses that increased IOP did not increase protein content of the aqueous. In contrast, PGD2 increased the IOP in both eyes; however, it significantly increased aqueous protein content of the experimental eye, indicating that increase in protein content of the aqueous and increase in IOP are not necessarily associated. None of the PGs tested in this study had any effect on pupil diameter or PMN entry into the aqueous. Therefore the classic signs of intraocular inflammation, i.e., increase in IOP, increase in protein content of the aqueous, miosis, and PMN entry into aqueous, are not necessarily associated and sequential, and PGs do not induce all signs of inflammation.
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PMID:The effect of intravitreal and topical prostaglandins on intraocular inflammation. 705 5

Cyclooxygenase products of arachidonic acid, for example prostaglandins (PGs), prostacyclin, and thromboxane A2, mediate a wide range of physiological actions. Vasodilation, increased vascular permeability, platelet aggregation and its inhibition, and immunomodulation are some of the important biological actions of cyclooxygenase products (1). Depending on type and dose, PGs cause vasodilation, increase or decrease intraocular pressure, and disrupt the blood-aqueous barrier (2, 3). These actions also vary qualitatively and quantitatively with the animal species. Prostaglandins, like any biological molecule, must act by binding with their specific receptors. Coleman and coworkers (4, 5), from a series of studies with PG agonists and antagonists in vascular and non-vascular smooth muscle preparations, classified PG receptors. This classification led to a greater appreciation of the relationship between PG actions and specific PG receptors in various tissues. Ocular actions of PGs linked with specific PG receptors are far from being clear. In this communication we will review our work on PG binding sites in ocular tissues and PG receptors coupled to adenylyl cyclase or phosphoinositidase C signal transduction pathways in ocular tissues of various animal species.
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PMID:Studies on prostanoid receptors in ocular tissues. 820 23

The use of natural prostaglandins (PG), such as PGD2, PGE2, PGF2 alpha, and PGI2, for treating glaucoma is limited by their ocular side effects. One approach to achieve the required separation of ocular hypotensive activity from side effects is to employ ester prodrugs. From a novel series of 11- and 15-mono and 11,15-diacyl esters of PGF2 alpha we identified prodrugs where PGF2 alpha formation rates in the iris-ciliary body exceeded those in the conjunctiva, sclera, and corneal endothelium. Compared to PGF2 alpha-1-isopropyl ester the ocular tissue hydrolysis rates of the 11-monopivaloyl, the 11,15-dipivaloyl ester and the 1,11-lactone were up to 1000 fold less. Despite this large disparity in hydrolysis rates, the pivaloyl esters and the 1,11-lactone were potent ocular hypotensives in our animal models. In studying prostaglandin analogs, we found that a diverse variety of prostanoid receptor selective agonists lowered intraocular pressure in dogs and/or monkeys. These included DP-, EP1-, EP2-, EP3-, and FP-receptor selective compounds. These findings were surprising and prompted us to re-examine the receptor selectivity of these agonists by radioligand binding studies. Using radiolabelled PGE2, 17-phenyl PGF2 alpha, and sulprostone we were able to confirm the selectivity of the agonists currently used for receptor characterization directly by radioligand binding competition studies. It appears that multiple prostanoid receptor subtypes may be involved in regulating intraocular pressure.
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PMID:Studies on the ocular hypotensive effects of prostaglandin F2 alpha ester prodrugs and receptor selective prostaglandin analogs. 820 25

AL-5848 (5Z,13E)-(9 S,11R,15S)-9,11,15-trihydroxy-5,13-prostadienoic acid) is the carboxylic acid of travoprost (AL-6221), a single (+)-isomer of (+/-)-fluprostenol, an FP-class prostaglandin agonist which lowers intraocular pressure. We have prepared a radioligand from this selective prostaglandin and demonstrated its utility for studying the pharmacology and autoradiographic location of the FP-receptor. Specific [3H]AL-5848 binding (84% of total) was linearly related to bovine corpus luteum tissue concentration and reached equilibrium within 275 min at 23 degrees C. Scatchard analysis of saturation isotherms indicated interaction of [3H]AL-5848 with a single class of high-affinity (dissociation constant, Kd, = 33.8+/-2.9 nM, n = 4) and saturable (Bmax = 37.3+/-3.0 pmol (g wet weight tissue)(-1)) FP receptor-binding sites in bovine corpus luteum. Specific [3H]AL-5848 binding was potently inhibited by the FP-receptor ligands 16-phenoxyPGF2alpha (inhibition constant Ki = 17.3 nM); cloprostenol (Ki = 56.8 nM); 17-phenyl PGF2alpha (Ki = 87.0 nM); AL-5848 (Ki = 52.1 nM); PGF2alpha (Ki = 195 nM); PHXA85 (Ki = 223 nM); (n = 3-11) but very weakly by PGD2, ZK118182, BW245C, PGE2, PGI2 and U-46619. The pharmacology of specific [3H]AL-5848 binding correlated well with the pharmacology of [3H]PGF2alpha binding in the bovine corpus luteum preparation (r = 0.98, n = 14, P<0.0001) and also with functional responses in Swiss 3T3 and rat vascular smooth muscle cells (A7r5) (r = 0.96) expressing FP receptors. Autoradiographic studies revealed high levels of specific FP-receptor binding with [3H]AL-5848 on granulosa cells in the bovine corpus luteum sections, and on longitudinal ciliary muscle, the ciliary process, the iris sphincter and the retina in eye sections from man. These studies show [3H]AL-5848 to be a high-affinity agonist radioligand capable of selectively labelling the FP prostaglandin receptor.
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PMID:[3H]AL-5848 ([3H]9beta-(+)-Fluprostenol). Carboxylic acid of travoprost (AL-6221), a novel FP prostaglandin to study the pharmacology and autoradiographic localization of the FP receptor. 1045 45

Our hypothesis is that the proteins in aqueous humor may be involved in the regulation of outflow facility through the trabecular meshwork and uveoscleral meshwork. In this study, we analyzed the profile of heparin-binding proteins present in porcine aqueous humor to identify and characterize secretory proteins with a binding affinity for heparin. A single step involving heparin-sepharose affinity chromatography of porcine aqueous humor yielded a approximately 60 kDa protein as the major heparin-binding species. This protein was specifically eluted from the column by heparin. The N-terminal sequence and immunological cross reactivity of this protein confirmed its identity as antithrombin III. Aqueous humor from different species, as well as cells from human trabecular meshwork, Schlemm's canal, and lens epithelium, contained detectable amounts of antithrombin III. Based on its known anticoagulative function in endothelial cells and effects on the production of prostacyclin, it is reasonable to speculate that antithrombin III present in aqueous humor might influence the physiology of the trabecular and uveoscleral meshwork and thereby regulate intraocular pressure.
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PMID:Antithrombin III, a serpin family protease inhibitor, is a major heparin binding protein in porcine aqueous humor. 1087 94


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