The Prostanoid EP<sub>2</sub>Receptor Agonist Butaprost Increases Uveoscleral Outflow in the Cynomolgus Monkey

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

doi:10.1167/iovs.05-1627

Cited by 89 publications

(73 citation statements)

References 29 publications

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“…It seems that the long-term 24-hour travoprost efficacy is only slightly greater than that reported over the short-term (with up to 3 mo follow-up). Possible reasons for this small difference include the mechanism of action of travoprost, which involves remodeling of the extracellular matrix, [30][31][32] hence it is logical to assume a small increase in efficacy after the first few months of treatment.…”

Section: Discussionmentioning

confidence: 99%

Long-term 24-hour Intraocular Pressure Control With Travoprost Monotherapy in Patients With Primary Open-angle Glaucoma

Riva

Katsanos

Floriani

et al. 2014

Journal of Glaucoma

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Purpose: The aim of the study was to evaluate the long-term 24-hour intraocular pressure (IOP) efficacy of travoprost monotherapy in primary open-angle glaucoma patients.Patients and Methods: A total of 36 previously untreated primary open-angle glaucoma patients were enrolled in this 5-year study.Patients underwent an untreated 24-hour IOP evaluation. Subsequently all patients were assigned to topical therapy with travoprost 0.004% eye-drops preserved with benzalkonium chloride (Travatan, Alcon Laboratories Inc., Fort Worth, TX) administered once in the evening (8:00 PM) in both eyes. All patients were then scheduled for a 24-hour IOP assessment approximately 12 months after the baseline visit. This schedule of follow-up was maintained for the whole duration of the trial. The predetermined range of target IOP reduction selected in this cohort of patients ranged between 20% and 30%.Results: A total of 34 patients completed all phases of the investigation. The mean survival time was 57.3 ± 2.0 months and the cumulative survival rate was 0.82 ± 0.6 at 60 months. Travoprost reduced the mean 24-hour IOP from 23.4 ± 1.7 mm Hg at baseline to 16.8 ± 2.4 mm Hg (28.4%), 16.8 ± 2.5 mm Hg (28.1%), 16.8 ± 2.4 mm Hg (28.5%), 16.7 ± 2.5 mm Hg (28.6%), and 16.9 ± 2.4 mm Hg (27.8%), respectively at the end of the first, second, third, fourth, and fifth year follow-up. No drug-related serious adverse events were registered during the study.Conclusions: The present study demonstrated the long-term 24-hour efficacy of travoprost for the treatment of primary open-angle glaucoma.Key Words: open-angle glaucoma, prostaglandin analogue, circadian intraocular pressure, travoprost (J Glaucoma 2014;23:535-540) R eduction of intraocular pressure (IOP) is the only currently available, evidence-based management strategy in patients affected with primary open-angle glaucoma (POAG). Most POAG patients will require lifelong medical therapy to avoid visual loss. The decision to select medical therapy options relies primarily on the efficacy of the available medications in various therapeutic trials. Sadly, most published studies only evaluate the short-term, daytime efficacy of medical therapy.Prostaglandin analogues have become a popular firstline therapy option for lowering IOP in POAG owing to their superior 24-hour efficacy, 1-6 convenient once-a-day administration, 5 and favorable systemic safety profile. 7 Travoprost is a synthetic prostaglandin F2a analogue that exerts its IOP-lowering effect through the prostaglandin FP receptors situated at the ciliary muscle 8 and the trabecular meshwork. 9 Travoprost is increasingly becoming a popular first-line monotherapy option for POAG patients 10 as there is cumulative evidence suggesting good quality of shortterm 24-hour IOP control with low fluctuation, especially with evening administration. 11-13 However, although several controlled studies have demonstrated the daytime short-term efficacy of travoprost monotherapy, [14][15][16] little is currently known about its long-term efficacy.As POA...

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Section: Discussionmentioning

confidence: 99%

Long-term 24-hour Intraocular Pressure Control With Travoprost Monotherapy in Patients With Primary Open-angle Glaucoma

Riva

Katsanos

Floriani

et al. 2014

Journal of Glaucoma

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“…Considering the fact that PGE 2 , a nonspecific EP receptor agonist, has been shown to have a strong potential for IOP reduction (Gabelt et al 2004), it is highly likely that this autacoid participates in the ocular hypotensive effect of epinephrine. It is suggested that the discussed effect can be achieved through the PGE 2 -induced increase of the uveoscleral outflow, but at present there is no definite evidence that PGE 2 increases this type of outflow, even though there are some data (Nilsson et al 2006) pointing to this possibility.…”

Section: Mechanism Of Actionmentioning

confidence: 97%

Autonomic drugs in the treatment of canine and feline glaucoma – Part I: Medications that lower intraocular pressure by increasing the outflow of aqueous humour

Maślanka¹

2014

Polish Journal of Veterinary Sciences

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One characteristic of the most common types of glaucoma is increased intraocular pressure (IOP), which has a damaging effect on optic nerve axons, leading to progressive loss of retinal ganglion cells. Therefore, ocular hypotensive drugs are the mainstay of pharmacological therapy for glaucoma. This review article, which is the first part of a two-part series, is dedicated to autonomic drugs which lower IOP by increasing the outflow of aqueous humour. These agents are subdivided into two groups: (a) drugs that lower IOP by increasing the trabecular outflow and the uveoscleral outflow (i.e. nonselective adrenergic agonists), and (b) medications that lower IOP by opening of the drainage angle and by increasing the conventional outflow via the trabecular outflow (i.e. parasympathomimetics). This paper summarizes the current state of knowledge on the mechanism of action of these drugs and their effect on IOP in dogs and cats. Moreover, it discusses possible undesirable side effects of these medications and presents the current ideas about their role and position in the medical management of glaucoma in small animals.

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“…Relaxation of TM cells as a result of a reduction of actin stress fibers and vinculin localization at focal adhesions was observed using such analogs [171]. Interest is increasing in the development of EP 2 and EP 4 receptor agonists for the treatment of POAG, with one such EP 2 agonist having been shown to reduce IOP by increasing both unconventional and conventional flow, facilitated by the relaxation of SC and by decrease in contractility and collagen deposition at the TM [172][173][174]. These effects are similar to those of traditional FP receptor agonists, however these, in contrast, may increase TM contractility.…”

Section: New Classes Of Drugmentioning

confidence: 99%

Open-angle glaucoma: therapeutically targeting the extracellular matrix of the conventional outflow pathway

O’Callaghan

Cassidy

Humphries

2017

Expert Opinion on Therapeutic Targets

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Introduction:Ocular hypertension in open-angle glaucoma is caused by a reduced rate of removal of aqueous humour (AH) from the eye, with the majority of AH draining from the anterior chamber through the conventional outflow pathway, comprising the trabecular meshwork (TM) and Schlemm's Canal. Resistance to outflow is generated, in part, by the extracellular matrix (ECM) of the outflow tissues. Current pressure-lowering topical medications largely suppress AH production, or enhance its clearance through the unconventional pathway. However, therapies targeting the ECM of the conventional pathway in order to decrease intraocular pressure have become a recent focus of attention. Areas covered: We discuss the role of ECM of the TM in outflow homeostasis and its relevance as a target for glaucoma therapy, including progress in development of topical eye formulations, together with gene therapy approaches based on inducible, virally-mediated expression of matrix metalloproteinases to enhance aqueous outflow. Expert opinion: There remains a need for improved glaucoma medications that more specifically act upon sites causative to glaucoma pathogenesis. Emerging strategies targeting the ECM of the conventional outflow pathway, or associated components of the cytoskeleton of TM cells, involving new pharmacological formulations or genetically-based therapies, are promising avenues of future glaucoma treatment. ARTICLE HISTORY

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The Prostanoid EP₂Receptor Agonist Butaprost Increases Uveoscleral Outflow in the Cynomolgus Monkey

Cited by 89 publications

References 29 publications

Long-term 24-hour Intraocular Pressure Control With Travoprost Monotherapy in Patients With Primary Open-angle Glaucoma

Long-term 24-hour Intraocular Pressure Control With Travoprost Monotherapy in Patients With Primary Open-angle Glaucoma

Autonomic drugs in the treatment of canine and feline glaucoma – Part I: Medications that lower intraocular pressure by increasing the outflow of aqueous humour

Open-angle glaucoma: therapeutically targeting the extracellular matrix of the conventional outflow pathway

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The Prostanoid EP2Receptor Agonist Butaprost Increases Uveoscleral Outflow in the Cynomolgus Monkey

Cited by 89 publications

References 29 publications

Long-term 24-hour Intraocular Pressure Control With Travoprost Monotherapy in Patients With Primary Open-angle Glaucoma

Long-term 24-hour Intraocular Pressure Control With Travoprost Monotherapy in Patients With Primary Open-angle Glaucoma

Autonomic drugs in the treatment of canine and feline glaucoma – Part I: Medications that lower intraocular pressure by increasing the outflow of aqueous humour

Open-angle glaucoma: therapeutically targeting the extracellular matrix of the conventional outflow pathway

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The Prostanoid EP₂Receptor Agonist Butaprost Increases Uveoscleral Outflow in the Cynomolgus Monkey