The mechanism of action of prostaglandins on uveoscleral outflow

Schachtschabel, Undine; Lindsey, James D.; Weinreb, Robert N.

doi:10.1097/00055735-200004000-00008

Cited by 110 publications

(54 citation statements)

References 26 publications

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“…(Bill and Maepea 1994;Schachtschabel et al 2000;Weinreb 2000;Weinreb et al 2002) Modulation of the trabecular outflow resistance is responsible for most of the regulation of intraocular pressure (IOP). (Brubaker 1970;Brubaker 1991) In openangle glaucoma, sustained increases in the trabecular outflow resistance commonly result in elevated intraocular pressure (IOP).…”

Section: Introductionmentioning

confidence: 99%

Extracellular matrix in the trabecular meshwork

Acott

Kelley

2008

Experimental Eye Research

424

443

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The extracellular matrix (ECM) of the trabecular meshwork (TM) is thought to be important in regulating intraocular pressure (IOP) in both normal and glaucomatous eyes. IOP is regulated primarily by a fluid resistance to aqueous humor outflow. However, neither the exact site nor the identity of the normal resistance to aqueous humor outflow has been established. Whether the site and nature of the increased outflow resistance, which is associated with open-angle glaucoma, is the same or different from the normal resistance is also unclear.The ECMs of the TM beams, juxtacanalicular region (JCT) and Schlemm's canal (SC) inner wall are comprised of fibrillar and non-fibrillar collagens, elastin-containing microfibrils, matricellular and structural organizing proteins, glycosaminoglycans (GAGs) and proteoglycans. Both basement membranes and stromal ECM are present in the TM beams and JCT region. Cell adhesion proteins, cell surface ECM receptors and associated binding proteins are also present in the beams, JCT and SC inner wall region.The outflow pathway ECM is relatively dynamic, undergoing constant turnover and remodeling. Regulated changes in enzymes responsible for ECM degradation and biosynthetic replacement are observed. IOP homeostasis, triggered by pressure changes or mechanical stretching of the TM, appears to involve ECM turnover. Several cytokines, growth factors and drugs, which affect the outflow resistance, change ECM component expression, mRNA alternative splicing, cellular cytoskeletal organization or all of these. Changes in ECM associated with open-angle glaucoma have been identified.

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Section: Introductionmentioning

confidence: 99%

Extracellular matrix in the trabecular meshwork

Acott

Kelley

2008

Experimental Eye Research

424

443

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“…Extensive studies have demonstrated prostaglandin-related decreases in TM cell contractility and outflow resistance of organ-cultured anterior segments [121][122][123]. The overall mechanisms through which prostaglandins enhance AH outflow remain to be fully elucidated; however, it is widely accepted that remodeling of the ECM plays a part [124][125][126][127], and it is of note that upregulation in MMP expression, through activation of prostaglandin receptors, may be involved [89,128]. However, the unique receptor profile for each analog may induce ECM modulation via different cascade pathways.…”

Section: Traditional Topical Medications In the Management Of Glaucomamentioning

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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“…Prostaglandins are well known to lower IOP by remodeling the extracellular matrix in the ciliary muscle, thereby increasing the uveoscleral outflow. [10][11][12] In the late 1980s, Emi et al suggested that a negative pressure gradient between the suprachoroidal space and anterior chamber may be preferable for directing aqueous. 13 The CyPass Micro-Stent utilizes this platform; its implantation is ab interno and uses the same clear corneal incision as the cataract surgery.…”

Section: Cypass Micro-stentmentioning

confidence: 99%

Minimally Invasive Glaucoma Surgery and CyPass® Micro-Stent—A New Era in Glaucoma Surgery

Mosaed¹

2017

US Ophthalmic Review

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In the largest randomized clinical trial to date on a minimally invasive glaucoma surgery device, the CyPass ® Micro-Stent was able to lower intraocular pressure (IOP) more than was modern cataract surgery (phacoemulsification and intraocular lens implantation) alone, and should be considered for patients with mild to moderate glaucoma already scheduled to undergo phacoemulsification surgery. The two-year outcomes of the COMPASS study found mean IOP reductions of 7.4 mmHg in the CyPass Micro-Stent group and no vision-threatening adverse events; more than 98% of subjects in the CyPass Micro-Stent group achieved 20/40 or better best-corrected visual acuity.

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The mechanism of action of prostaglandins on uveoscleral outflow

Cited by 110 publications

References 26 publications

Extracellular matrix in the trabecular meshwork

Extracellular matrix in the trabecular meshwork

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

Minimally Invasive Glaucoma Surgery and CyPass® Micro-Stent—A New Era in Glaucoma Surgery

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