Aqueous Humor Dynamics in Monkeys after Topical 8-Iso PGE<sub>2</sub>

Gabelt, B’Ann T.; Seeman, Jennifer L.; Podos, Steven M.; Mittag, Thomas W.; Kaufman, Paul L.

doi:10.1167/iovs.03-0911

Cited by 18 publications

(10 citation statements)

References 31 publications

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“…Prostaglandin-induced IOP reduction has been reported by different groups in different species, such as cat, rabbit and monkeys [48][49][50][51][52][53]. However, there are enormous species differences.…”

Section: Prostaglandins and Outflow Facilitymentioning

confidence: 99%

Endogenous bioactive lipids and the regulation of conventional outflow facility

Wan

Woodward

Stamer

2008

Expert Review of Ophthalmology

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SummaryPerturbation of paracrine signaling within the human conventional outflow pathway influences tissue homeostasis and outflow function. For example, exogenous introduction of the bioactive lipids, sphingosine-1-phosphate, anandamide or prostaglandin F 2α , to conventional outflow tissues alters the rate of drainage of aqueous humor through the trabecular meshwork, and into Schlemm's canal. This review summarizes recent data that characterizes endogenous bioactive lipids, their receptors and associated signaling partners in the conventional outflow tract. We also discuss the potential of targeting such signaling pathways as a strategy for the development of therapeutics to treat ocular hypertension and glaucoma.

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Section: Prostaglandins and Outflow Facilitymentioning

confidence: 99%

Endogenous bioactive lipids and the regulation of conventional outflow facility

Wan

Woodward

Stamer

2008

Expert Review of Ophthalmology

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“…The ocular hypotensive response to FP-agonists is unusual, in that it improves over time with multiple dosing. [5][6][7] This enhanced response supports the idea that the chronic use of FP-agonists induces a structural and/or molecular change within the outflow pathway that acts synergistically with the subsequent administration of FP-agonists to lower IOP. FP-agonists lead to a loss of connective tissue within the ciliary body and increase the expression and/or secretion of MMPs.…”

Section: Discussionmentioning

confidence: 61%

“…3,4 However, early animal studies demonstrated that this response is unusual, in that the response to FP-receptor agonists improves with multiple dosing over time. [5][6][7] This enhanced functional response supports the idea that the chronic use of FP-receptor agonists induces a structural and/or molecular change within the outflow pathway that acts synergistically with a later administration of an FP-receptor agonist to lower IOP.…”

mentioning

confidence: 60%

Latanoprost-Induced Changes in Rat Intraocular Pressure: Direct or Indirect?

Husain

Yates

Crosson

2008

Journal of Ocular Pharmacology and Therapeutics

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Introduction: The topical application of prostaglandin F 2␣ (FP)-receptor agonists has been shown to significantly lower intraocular pressure (IOP) in humans and is now considered the first-line treatment for ocular hypertension. Despite the prominent role FP-receptor agonists play in the treatment of glaucoma, our understanding of how these agents lower IOP remains incomplete. The present study was designed to evaluate the role of matrix metalloproteinase (MMP) activation and the cytokine, tumor necrosis factor alpha (TNF-␣), in latanoprost-induced changes in IOP. Methods: Changes in IOP following an acute topical administration of latanoprost (60 ng) in normotensive Brown Norway rats were evaluated by means of a commercially available rebound tonometer. To examine the role of MMPs and TNF-␣ in this response, the rats were pretreated with a broad-spectrum MMP inhibitor, GM-6001 (100 g), or the TNF-␣ inhibitor, thalidomide (25 g). Results: The topical administration of latanoprost (60 ng) alone produced a biphasic change in ipsilateral IOP: an initial hypertension (4.21 Ϯ 0.52), followed by a prolonged hypotension (Ϫ4.79 Ϯ 0.65). In rats, pretreatment with GM-6001 blocked the latanoprost-induced reduction in IOP but did not prevent the initial rise in IOP. Pretreatment with thalidomide also blocked the ocular hypotension induced by latanoprost; however, thalidomide pretreatment enhanced the duration of the initial hypertension. Conclusions: These results provide evidence that the secretion and activation of MMPs and the release of TNF-␣ play a central role in the ocular hypotension induced by FP-agonists. The administration of FP-agonists appears to lower IOP directly by inducing the activation of MMPs within the ciliary body, leading to improved uveoscleral outflow and indirectly through the release of TNF-␣ within the ciliary body. Secreted TNF-␣ may then activate TNF-receptors in the uvea and trabecular meshwork, increasing both uveoscleral and conventional outflow.

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“…In ocular tissues, there is evidence that 8-isoPGE 2 can lower intraocular pressure in normotensive rabbits [15] and monkeys and increase total outflow facility in cynomolgus monkeys [16]. Evidence from our laboratories demonstrate that 8-isoPGE 2 can regulate the release of exogenously applied [ 3 H]norepinephrine and [ 3 H]dopamine release in mammalian anterior uvea [17,18] and retina [19] respectively, in vitro.…”

Section: Introductionmentioning

confidence: 94%

Role of Prostanoid Production and Receptors in the Regulation of Retinal Endogenous Amino Acid Neurotransmitters by 8-Isoprostaglandin E2, Ex Vivo

Zhao¹,

Destache²,

Ohia³

et al. 2009

Neurochem Res

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The role of enzymes and receptors of the prostanoid pathway in the inhibitory effect of 8-isoprostaglandin E2 (8-isoPGE2) on endogenous amino acid neurotransmitter levels was examined, ex vivo. Freshly isolated bovine eyeballs were injected intravitreally with IsoPs, incubated in Krebs buffer for 30 min and retina prepared for HPLC-ECD detection of amino acids. 8-isoPGE2 attenuated retinal glutamate and its metabolite, glutamine and glycine in a concentration-dependent manner. The nonselective cyclooxygenase (COX)-inhibitor, flurbiprofen, COX-2 selective inhibitor, NS-398 and thromboxane (Tx) synthase inhibitor, furegrelate had no effect on both basal amino acid levels and the inhibitory effects of 8-isoPGE2 (1-100 μM) on the retinal amino acids. Whereas the TP-receptor antagonist SQ-29548(10 μM) exhibited no effect, SC-19220(EP1; 30 μM), AH-6809(EP(1-3); 30 μM) and AH-23848(EP4; 30 μM) reversed the inhibitory effects of 8-isoPGE2 (0.01-100 μM) on glutamate, glutamine and glycine levels. We conclude that prostanoid EP-receptors regulate the inhibitory effect of 8-isoPGE2 on basal levels of endogenous amino acids in bovine retina, ex vivo.

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Aqueous Humor Dynamics in Monkeys after Topical 8-Iso PGE₂

Abstract: The present findings are consistent with lowering of IOP by 8-iso PGE(2), primarily by increasing Fu. A direct effect on the trabecular meshwork was not indicated by these in vivo studies.

Cited by 18 publications

References 31 publications

Endogenous bioactive lipids and the regulation of conventional outflow facility

Endogenous bioactive lipids and the regulation of conventional outflow facility

Latanoprost-Induced Changes in Rat Intraocular Pressure: Direct or Indirect?

Role of Prostanoid Production and Receptors in the Regulation of Retinal Endogenous Amino Acid Neurotransmitters by 8-Isoprostaglandin E2, Ex Vivo

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Aqueous Humor Dynamics in Monkeys after Topical 8-Iso PGE2

Abstract: The present findings are consistent with lowering of IOP by 8-iso PGE(2), primarily by increasing Fu. A direct effect on the trabecular meshwork was not indicated by these in vivo studies.

Cited by 18 publications

References 31 publications

Endogenous bioactive lipids and the regulation of conventional outflow facility

Endogenous bioactive lipids and the regulation of conventional outflow facility

Latanoprost-Induced Changes in Rat Intraocular Pressure: Direct or Indirect?

Role of Prostanoid Production and Receptors in the Regulation of Retinal Endogenous Amino Acid Neurotransmitters by 8-Isoprostaglandin E2, Ex Vivo

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Aqueous Humor Dynamics in Monkeys after Topical 8-Iso PGE₂