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TIMP1, TIMP2, and TIMP4 are increased in aqueous humor from primary open angle glaucoma patients


Ashworth Briggs, EL and Toh, TY and Eri, RD and Hewitt, A and Cook, AL, TIMP1, TIMP2, and TIMP4 are increased in aqueous humor from primary open angle glaucoma patients, Molecular Vision, 21 pp. 1162-1172. ISSN 1090-0535 (2015) [Refereed Article]

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Copyright 2015 Molecular Vision

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Purpose: Elevated intraocular pressure (IOP) is the only known modifiable risk factor for primary open angle glaucoma (POAG), and it can be caused by reduced aqueous humor outflow from the anterior chamber. Outflow is predominantly regulated by the trabecular meshwork, consisting of specialized cells within a complex extracellular matrix (ECM). An imbalance between ECM-degrading matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs) within the trabecular meshwork is thought to contribute to POAG. This study aimed to quantify levels of TIMPs and MMPs in aqueous humor samples from glaucomatous and non-glaucomatous eyes, analyze MMP/TIMP ratios, and correlate results with age, IOP, and Humphrey’s visual field pattern standard deviation (PSD).

Methods: Aqueous humor samples were collected from 26 non-glaucomatous control subjects before cataract surgery and 23 POAG patients undergoing trabeculectomy or cataract surgery. Analyte concentrations were measured using multiplexed immunoassays. Statistical significance was assessed with Mann–Whitney U tests, and Spearman’s method was used to assess correlations with age, IOP, and PSD.

Results: Concentrations of TIMP1 (p = 0.0008), TIMP2 (p = 0.002), TIMP4 (p = 0.002), and MMP2 (p = 0.020) were significantly increased in aqueous humor samples from POAG versus cataract samples. For the majority of MMP/TIMP molar ratios calculated for the cataract group, TIMPs outweighed MMPs. In POAG, molar ratios of MMP2/TIMP1 (p = 0.007) and MMP9/TIMP1 (p = 0.005) showed a significant decrease, corresponding to an elevated excess of TIMPs over MMPs in POAG compared to cataract samples. Conversely, MMP2/TIMP3 (p = 0.045) and MMP3/TIMP3 (p = 0.032) molar ratios increased. Several MMP/TIMP molar ratios correlated with IOP (r = 0.476–0.609, p = 0.007–0.034) and PSD (r = -0.482 to −0.655, p = 0.005–0.046) in POAG samples and with age in cataract control samples.

Conclusions: An imbalance among MMPs and TIMPs was found in glaucomatous aqueous humor samples, with a shift toward raised TIMP levels. This may result in the inhibition of MMP activity, leading to an altered ECM composition in the TM and thereby contributing to increased outflow resistance.

Item Details

Item Type:Refereed Article
Keywords:glaucoma, MMP, TIMP
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Vision science
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Ashworth Briggs, EL (Mrs Esther Ashworth Briggs)
UTAS Author:Eri, RD (Associate Professor Raj Eri)
UTAS Author:Hewitt, A (Professor Alex Hewitt)
UTAS Author:Cook, AL (Associate Professor Tony Cook)
ID Code:103504
Year Published:2015
Web of Science® Times Cited:31
Deposited By:Wicking Dementia Research and Education Centre
Deposited On:2015-10-14
Last Modified:2017-11-06

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