Elevated Matrix Metalloproteinase in Aqueous Humor in Patients with Open-Angle Glaucoma

Hyo Won Kim; Dong Hyun Jee; Jin A Choi

doi:10.3341/jkos.2016.57.4.601

Journal List > J Korean Ophthalmol Soc > v.57(4) > 1010558

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Kim, Jee, and Choi: Elevated Matrix Metalloproteinase in Aqueous Humor in Patients with Open-Angle Glaucoma

Original Article

J Korean Ophthalmol Soc 2016;57(4):601-606.

Published online: 3 September 2016

DOI: https://doi.org/10.3341/jkos.2016.57.4.601

Elevated Matrix Metalloproteinase in Aqueous Humor in Patients with Open-Angle Glaucoma

Hyo Won Kim, MD, Dong Hyun Jee, MD, Jin A Choi, MD, PhD

Department of Ophthalmology and Visual Science, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea

Address reprint requests to Jin A Choi, MD, PhD Department of Ophthalmology, The Catholic University of Korea St. Vincent's Hospital #93 Jungbu-daero, Paldal-gu, Suwon 16247, Korea Tel: 82-31-249-8310, Fax: 82-31-251-6225 E-mail: jinah616@hanmail.net

Received 15 October 2015 Revised 18 December 2015 Accepted 13 February 2016

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

To compare the aqueous concentrations of cytokines in glaucomatous eyes with those of normal controls and to characterize the clinical factors associated with aqueous cytokine concentration.

Methods

In this cross-sectional study, aqueous humor samples were collected from 54 eyes of 54 patients (34 medically treated primary open angle glaucoma and 20 normal controls) during cataract surgery from January 2014 to January 2015. Glaucoma patients were divided into two groups: patients using prostaglandin analogue for more than 6 months (prostaglandin F₂α analogue [PGA] user) and patients with no experience of PGA use (PGA non-user). The levels of cytokines (matrix metalloproteinase [MMP]1, MMP9, MMP3, vascular endothelial growth factor, interleukin [IL]-1, IL-8, tumor necrosis factor [TNF]-α) in the aqueous of glaucoma and control subjects were quantified using a multiplex cytokine analysis.

Results

Aqueous humor collected from the glaucoma patients exhibited significantly increased concentrations of MMP1 (p = 0.002) and MMP9 (p = 0.026). Among glaucoma patients, PGA users showed significantly higher level of MMP 9 compared with PGA non-users (p = 0.003). In the univariate and multivariate linear regression analyses, PGA use (ß = 0.351, p = 0.027) and vertical cup-to disc ratio (ß = −0.401, p = 0.013) were the significant risk factors associated with the level of MMP9.

Conclusions

Primary open-angle glaucoma showed increased aqueous levels of MMP1 and MMP9. Especially, PGA use for longer than 6 months was associated with increased level of MMP9.

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Keywords: Aqueous humor, Cytokines, Glaucoma, Matrix metalloproteinase, Prostaglandin

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Figure 1.

Comparisons of the aqueous concentrations of matrix metalloproteinase 1, 3, and 9 between glaucoma patients and normal controls. All the comparisons were performed by independent t-test. MMP = matrix metalloproteinase.

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Table 1.

Clinical characteristics of glaucoma patients and normal controls

	Glaucoma (n = 34)	Normal Control (n = 20)	p-value
Age (years)	70.1 ± 11.7	64.4 ± 16.8	0.326
Sex (% of female)	27/50	23/35	0.196
Laterality (% of right)	25/50	21/35	0.246
Spherical equivalent (diopter)	−1.4 ± 3.0	−1.7 ± 3.6	0.673
Axial length (mm)	23.4 ± 0.7	23.7 ± 1.5	0.216
Vertical cup-to disc ratio	0.7 ± 0.1	0.4 ± 0.1	<0.001
Preoperative IOP (mm Hg)	13.9 ± 3.4	13.2 ± 3.4	0.350
Postoperative 1 day IOP (mm Hg)	14.0 ± 4.8	13.0 ± 4.3	0.312
Postoperative 1 week IOP (mm Hg)	11.8 ± 4.7	11.7 ± 4.3	0.896

Values are presented as mean ± SD unless otherwise indicated.

IOP = intraocular pressure.

Table 2.

Comparison of clinical characteristics and aqueous cytokine concentrations between glaucoma patients using prostaglandin analogues for longer than 6 months and patients with no experience of prostaglandin analogues

	PGA user (n = 21)	PGA non-user (n = 13)	p-value
Clinical characteristics
Age (years)	67.7 ± 13.6	74.2 ± 6.8	0.180
Average RNFL thickness (μm)	77.0 ± 22.5	80.53 ± 17.9	0.787
Axial length (mm)	23.3 ± 0.55	23.57 ± 0.97	0.181
Vertical cup-to disc ratio	0.73 ± 0.17	0.73 ± 0.10	0.775
Preoperative IOP (mm Hg)	13.8 ± 3.0	14.6 ± 5.3	0.649
Postoperative 1 day IOP (mm Hg)	12.5 ± 5.0	10.6 ± 4.1	0.699
Postoperative 1 week IOP (mm Hg)	12.5 ± 5.0	10.6 ± 4.1	0.243
Number of anti-glaucoma eyedrops (number)	1.5 ± 0.9	0.8 ± 0.6	0.029
Use of beta-blocker (%)	42.8	46.1	0.565
Use of carbonid anhydrase inhibitor (%)	28.6	30.7	0.594
Use of α-selective adrenergic drugs (%)	23.8	23.1	0.648
Use of miotic agents (%)	0.0	7.7	0.382
Duration of anti-glaucoma eyedrops (months)	18.2 ± 22.9	26.5 ± 34.1	0.960
Duration of PGA (months)	18.3 ± 22.8	0.0 ± 0.0	0.003
Aqueous cytokine concentration
MMP1 (pg/mL)	6.7 ± 6.2	5.9 ± 8.7	0.420
MMP9 (pg/mL)	90.7 ± 73.1	40.3 ± 47.2	0.003
VEGF (pg/mL)	67.0 ± 46.2	42.3 ± 27.4	0.275
MMP3 (pg/mL)	1251.5 ± 1078.0	396.6 ± 604.6	0.081
IL-1 (pg/mL)	0.0 ± 0.0	0.0 ± 0.0	N/A
IL-8 (pg/mL)	13.2 ± 9.5	6.9 ± 3.6	0.058
TNF-alpha (pg/mL)	0.0 ± 0.0	0.1 ± 0.1	0.588

Values are presented as mean ± SD unless otherwise indicated.

PGA = prostaglandina analogues; RNFL = retinal nerve fiber layer; IOP = intraocular pressure; MMP = matrix metalloproteinase; VEGF = vascular endothelial growth factor; IL = interleukin; TNF = tumor necrosis factor; N/A = not applicable.

Table 3.

Clinical factors affecting aqueous concentration of MMP9 in glaucoma patients

Parameters	Univariate				Multivariate
Parameters	B	SE	β	p-value	B	SE	β	p-value
Age	−0.682	1.061	−0.113	0.525
Sex	15.21	24.75	0.108	0.543
PGA user	50.42	22.8	0.364	0.034	48.54	20.93	0.351	0.027
Axial length	−5.92	16.06	−0.066	0.715
Preoperative IOP	0.179	3.64	0.009	0.961
Average RNFL thickness	0.533	0.667	0.152	0.431
Duration of PGA	−0.047	0.621	−0.090	0.613
Number of anti-glaucoma eyedrops	−5.818	13.68	−0.075	0.674
Vertical cup-to disc ratio	−198.8	77.61	−0.412	0.015	−193.10	72.83	−0.401	0.013

MMP = matrix metalloproteinase; B = unstandardized coefficient; SE = spherical equivalent; β = standardized β PGA = prostaglandin analogue; IOP = intraocular pressure; RNFL = retinal nerve fiber layer.

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