The prostanoid EP2 receptor agonist butaprost increases uveoscleral outflow in the cynomolgus monkey

Siv F E Nilsson, Enken Drecoll, Elke Lütjen-Drecoll, Carol B Toris, Achim H P Krauss, Alexander Kharlamb, Amelia Nieves, Teresa Guerra, David F. Woodward

Research output: Contribution to journalArticle

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Abstract

PURPOSE. To investigate the ocular hypotensive effect of the prostanoid EP2 receptor agonist butaprost and to establish its mechanism of action. METHODS. All experiments were performed in cynomolgus monkeys after topical application of butaprost (0.1%). The effects of butaprost on aqueous humor flow were determined by fluorophotometry. Total outflow facility was measured by the two-level, constant-pressure perfusion method, and uveoscleral outflow was determined by perfusion of FITC-labeled dextran through the anterior chamber. Effects on ocular morphology were studied after tissue fixation with transcardial perfusion by paraformaldehyde and immersion fixation of the globe, in animals subjected to long-term treatment with butaprost. Conscious ocular normotensive monkeys and monkeys with unilateral ocular hypertension were used for intraocular pressure (IOP) studies. RESULTS. Butaprost had no significant effect on aqueous humor flow or total outflow facility in ocular normotensive monkeys. Uveoscleral outflow was significantly higher in the butaprost treated eyes than in vehicle treated eyes, 1.03 ± 0.20 vs. 0.53 ± 0.18 μL · min-1. After a 1-year treatment with butaprost, the morphology of the ciliary muscle was changed, showing increased spaces between ciliary muscle bundles and the apparent formation of new outflow channels. In many instances, changes were observed in the trabecular meshwork as well. Butaprost, in a single 0.1% dose, decreased IOP significantly in ocular normotensive monkeys and reduced IOP in laser-induced glaucomatous monkey eyes to the same level as that in the ocular normotensive contralateral eyes. CONCLUSIONS. The prostanoid EP2 receptor agonist butaprost appears to lower IOP by increasing uveoscleral outflow, according to both physiological and morphologic findings. Although the prostanoid EP2 receptor is structurally and functionally distinct from the FP receptor, the effects of EP2 and FP receptor stimulation on aqueous humor outflow are similar.

Original languageEnglish (US)
Pages (from-to)4042-4049
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume47
Issue number9
DOIs
StatePublished - Sep 1 2006

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Receptors, Prostaglandin E, EP2 Subtype
Macaca fascicularis
Haplorhini
Intraocular Pressure
Aqueous Humor
Perfusion
Fluorophotometry
butaprost
Tissue Fixation
Trabecular Meshwork
Muscles
Ocular Hypertension
Anterior Chamber
Immersion

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Nilsson, S. F. E., Drecoll, E., Lütjen-Drecoll, E., Toris, C. B., Krauss, A. H. P., Kharlamb, A., ... Woodward, D. F. (2006). The prostanoid EP2 receptor agonist butaprost increases uveoscleral outflow in the cynomolgus monkey. Investigative Ophthalmology and Visual Science, 47(9), 4042-4049. https://doi.org/10.1167/iovs.05-1627

The prostanoid EP2 receptor agonist butaprost increases uveoscleral outflow in the cynomolgus monkey. / Nilsson, Siv F E; Drecoll, Enken; Lütjen-Drecoll, Elke; Toris, Carol B; Krauss, Achim H P; Kharlamb, Alexander; Nieves, Amelia; Guerra, Teresa; Woodward, David F.

In: Investigative Ophthalmology and Visual Science, Vol. 47, No. 9, 01.09.2006, p. 4042-4049.

Research output: Contribution to journalArticle

Nilsson, SFE, Drecoll, E, Lütjen-Drecoll, E, Toris, CB, Krauss, AHP, Kharlamb, A, Nieves, A, Guerra, T & Woodward, DF 2006, 'The prostanoid EP2 receptor agonist butaprost increases uveoscleral outflow in the cynomolgus monkey', Investigative Ophthalmology and Visual Science, vol. 47, no. 9, pp. 4042-4049. https://doi.org/10.1167/iovs.05-1627
Nilsson, Siv F E ; Drecoll, Enken ; Lütjen-Drecoll, Elke ; Toris, Carol B ; Krauss, Achim H P ; Kharlamb, Alexander ; Nieves, Amelia ; Guerra, Teresa ; Woodward, David F. / The prostanoid EP2 receptor agonist butaprost increases uveoscleral outflow in the cynomolgus monkey. In: Investigative Ophthalmology and Visual Science. 2006 ; Vol. 47, No. 9. pp. 4042-4049.
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abstract = "PURPOSE. To investigate the ocular hypotensive effect of the prostanoid EP2 receptor agonist butaprost and to establish its mechanism of action. METHODS. All experiments were performed in cynomolgus monkeys after topical application of butaprost (0.1{\%}). The effects of butaprost on aqueous humor flow were determined by fluorophotometry. Total outflow facility was measured by the two-level, constant-pressure perfusion method, and uveoscleral outflow was determined by perfusion of FITC-labeled dextran through the anterior chamber. Effects on ocular morphology were studied after tissue fixation with transcardial perfusion by paraformaldehyde and immersion fixation of the globe, in animals subjected to long-term treatment with butaprost. Conscious ocular normotensive monkeys and monkeys with unilateral ocular hypertension were used for intraocular pressure (IOP) studies. RESULTS. Butaprost had no significant effect on aqueous humor flow or total outflow facility in ocular normotensive monkeys. Uveoscleral outflow was significantly higher in the butaprost treated eyes than in vehicle treated eyes, 1.03 ± 0.20 vs. 0.53 ± 0.18 μL · min-1. After a 1-year treatment with butaprost, the morphology of the ciliary muscle was changed, showing increased spaces between ciliary muscle bundles and the apparent formation of new outflow channels. In many instances, changes were observed in the trabecular meshwork as well. Butaprost, in a single 0.1{\%} dose, decreased IOP significantly in ocular normotensive monkeys and reduced IOP in laser-induced glaucomatous monkey eyes to the same level as that in the ocular normotensive contralateral eyes. CONCLUSIONS. The prostanoid EP2 receptor agonist butaprost appears to lower IOP by increasing uveoscleral outflow, according to both physiological and morphologic findings. Although the prostanoid EP2 receptor is structurally and functionally distinct from the FP receptor, the effects of EP2 and FP receptor stimulation on aqueous humor outflow are similar.",
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T1 - The prostanoid EP2 receptor agonist butaprost increases uveoscleral outflow in the cynomolgus monkey

AU - Nilsson, Siv F E

AU - Drecoll, Enken

AU - Lütjen-Drecoll, Elke

AU - Toris, Carol B

AU - Krauss, Achim H P

AU - Kharlamb, Alexander

AU - Nieves, Amelia

AU - Guerra, Teresa

AU - Woodward, David F.

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N2 - PURPOSE. To investigate the ocular hypotensive effect of the prostanoid EP2 receptor agonist butaprost and to establish its mechanism of action. METHODS. All experiments were performed in cynomolgus monkeys after topical application of butaprost (0.1%). The effects of butaprost on aqueous humor flow were determined by fluorophotometry. Total outflow facility was measured by the two-level, constant-pressure perfusion method, and uveoscleral outflow was determined by perfusion of FITC-labeled dextran through the anterior chamber. Effects on ocular morphology were studied after tissue fixation with transcardial perfusion by paraformaldehyde and immersion fixation of the globe, in animals subjected to long-term treatment with butaprost. Conscious ocular normotensive monkeys and monkeys with unilateral ocular hypertension were used for intraocular pressure (IOP) studies. RESULTS. Butaprost had no significant effect on aqueous humor flow or total outflow facility in ocular normotensive monkeys. Uveoscleral outflow was significantly higher in the butaprost treated eyes than in vehicle treated eyes, 1.03 ± 0.20 vs. 0.53 ± 0.18 μL · min-1. After a 1-year treatment with butaprost, the morphology of the ciliary muscle was changed, showing increased spaces between ciliary muscle bundles and the apparent formation of new outflow channels. In many instances, changes were observed in the trabecular meshwork as well. Butaprost, in a single 0.1% dose, decreased IOP significantly in ocular normotensive monkeys and reduced IOP in laser-induced glaucomatous monkey eyes to the same level as that in the ocular normotensive contralateral eyes. CONCLUSIONS. The prostanoid EP2 receptor agonist butaprost appears to lower IOP by increasing uveoscleral outflow, according to both physiological and morphologic findings. Although the prostanoid EP2 receptor is structurally and functionally distinct from the FP receptor, the effects of EP2 and FP receptor stimulation on aqueous humor outflow are similar.

AB - PURPOSE. To investigate the ocular hypotensive effect of the prostanoid EP2 receptor agonist butaprost and to establish its mechanism of action. METHODS. All experiments were performed in cynomolgus monkeys after topical application of butaprost (0.1%). The effects of butaprost on aqueous humor flow were determined by fluorophotometry. Total outflow facility was measured by the two-level, constant-pressure perfusion method, and uveoscleral outflow was determined by perfusion of FITC-labeled dextran through the anterior chamber. Effects on ocular morphology were studied after tissue fixation with transcardial perfusion by paraformaldehyde and immersion fixation of the globe, in animals subjected to long-term treatment with butaprost. Conscious ocular normotensive monkeys and monkeys with unilateral ocular hypertension were used for intraocular pressure (IOP) studies. RESULTS. Butaprost had no significant effect on aqueous humor flow or total outflow facility in ocular normotensive monkeys. Uveoscleral outflow was significantly higher in the butaprost treated eyes than in vehicle treated eyes, 1.03 ± 0.20 vs. 0.53 ± 0.18 μL · min-1. After a 1-year treatment with butaprost, the morphology of the ciliary muscle was changed, showing increased spaces between ciliary muscle bundles and the apparent formation of new outflow channels. In many instances, changes were observed in the trabecular meshwork as well. Butaprost, in a single 0.1% dose, decreased IOP significantly in ocular normotensive monkeys and reduced IOP in laser-induced glaucomatous monkey eyes to the same level as that in the ocular normotensive contralateral eyes. CONCLUSIONS. The prostanoid EP2 receptor agonist butaprost appears to lower IOP by increasing uveoscleral outflow, according to both physiological and morphologic findings. Although the prostanoid EP2 receptor is structurally and functionally distinct from the FP receptor, the effects of EP2 and FP receptor stimulation on aqueous humor outflow are similar.

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