Matrix Metalloproteinases and Their Inhibitors in Aqueous Humor of Patients with Pseudoexfoliation Syndrome/Glaucoma and Primary Open-Angle Glaucoma

Schlötzer‐Schrehardt, Ursula; Lommatzsch, Jürgen; Küchle, Michael; Konstas, Anastasios G. P.; Naumann, Gottfried O.H.

doi:10.1167/iovs.02-0365

Cited by 189 publications

(163 citation statements)

References 34 publications

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“…It has also been shown that MMP9 among several other MMPs are present in the aqueous humor and may be involved in mechanisms of IOP regulation. 74,75 In addition, several PACG-associated risk conferring variants have been identified in the membrane-type frizzled related protein (MFRP) gene, methylenetetrahydrofolate reductase (MTHFR) gene, and retinal homeobox gene CHX10. 76,77 MFRP and CHX10 are thought to be involved in the regulation of eye size and axial length of the eye.…”

Section: Nebmentioning

confidence: 99%

The genetic mechanisms of primary angle closure glaucoma

Ahram

Alward

Kuehn

2015

Eye

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Primary Angle Closure Glaucoma (PACG) is one of the most common types of glaucoma affecting over 15 million individuals worldwide. Family history and ethnicity are strongly associated with the development of the disease, suggesting that one or more genetic factors contribute to PACG. Although strictly heritable disease-causing mutations have not been identified, a number of recent association studies have pointed out genetic factors that appear to contribute to an individual's risk to develop PACG. In addition, genetic factors have been identified that modify PACG endophenotypes for example, axial length. Herein we review the current literature on this important topic.

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Section: Nebmentioning

confidence: 99%

The genetic mechanisms of primary angle closure glaucoma

Ahram

Alward

Kuehn

2015

Eye

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“…Furthermore, growth factors, metalloproteinases, and ET-1 have been shown to be involved in the pathobiology of PEX. [20][21][22] Some studies have suggested that ET-1 promotes synthesis and/or turnover of extracellular matrix that has a role in the pathogenesis of PEX. 23,24 In addition, increased concentrations of transforming growth factor beta 1 (TGF-b1), a powerful modulator of extracellular matrix formation, 25 have been identified in the aqueous humour of patients with PEX 26 and increased TGF-b1 synthesis has been related with increased levels of reactive oxygen species.…”

Section: Discussionmentioning

confidence: 99%

Protein carbonyl levels in the aqueous humour and serum of patients with pseudoexfoliation syndrome

Yağcı

Ersöz

Erdurmuş

et al. 2007

Eye

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Purpose Protein oxidation is an oxidative stress marker and the oxidation of proteins is analysed by measuring the carbonyl groups. Protein oxidation can have a role in the physiopathology of pseudoexfoliation (PEX) syndrome. The aim of this study was to investigate the protein oxidation in the aqueous humour and serum of cataract patients with and without PEX. Methods A multicenter study was carried out. Aqueous humour and serum samples were collected from patients who underwent routine cataract surgery. Patients were divided into PEX (n ¼ 29) and control (n ¼ 27) groups. Patients had no elevated intraocular pressure or glaucoma. Spectrophotometer was used to measure protein carbonyl (PC) levels in the samples. Results Mean PC concentration in the PEX aqueous (2.1871.51 nmol/l) and serum (119.62713.2 nmol/l) samples was significantly higher than that measured in the control aqueous (1.3170.47 nmol/l) and serum (105.857 11.76 nmol/l) samples, respectively (Po 0.001). Conclusion The increased PC levels in the aqueous humour and serum of PEX patients suggest that protein oxidation may play a role in the physiopathology of PEX.

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“…To this end, tissue inhibitors of metalloproteinases (TIMPs) are expressed in a manner similar to that of MMPs, while the ratios of MMP: TIMP determine the extent of ECM modulation [58,91]. Such ratios tend to be imbalanced in POAG [92][93][94][95], and may be indicative of dysfunctional ECM turnover. MMP proteins are often upregulated in glaucomatous AH; however, the activity of these proteins is reduced in comparison to cataract controls, likely reflective of MMP:TIMP imbalance [92,[96][97][98].…”

Section: Modulation Of Ecm Turnovermentioning

confidence: 99%

“…Such ratios tend to be imbalanced in POAG [92][93][94][95], and may be indicative of dysfunctional ECM turnover. MMP proteins are often upregulated in glaucomatous AH; however, the activity of these proteins is reduced in comparison to cataract controls, likely reflective of MMP:TIMP imbalance [92,[96][97][98]. Perfusion of ocular tissues with MMPs or MMP-activating compounds results in increased outflow facility, possibly the most convincing demonstration of ECM involvement in regulating outflow resistance [99][100][101][102].…”

Section: Modulation Of Ecm Turnovermentioning

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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Matrix Metalloproteinases and Their Inhibitors in Aqueous Humor of Patients with Pseudoexfoliation Syndrome/Glaucoma and Primary Open-Angle Glaucoma

Abstract: The findings suggest that complex changes in the local MMP-TIMP balance and reduced MMP activity in aqueous humor may promote the abnormal matrix accumulation characteristic of PEX syndrome and may be causally involved in the pathogenesis of both PEX glaucoma and POAG.

Cited by 189 publications

References 34 publications

The genetic mechanisms of primary angle closure glaucoma

The genetic mechanisms of primary angle closure glaucoma

Protein carbonyl levels in the aqueous humour and serum of patients with pseudoexfoliation syndrome

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

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