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. 2009 Jul;50(7):3203-9.
doi: 10.1167/iovs.08-2476. Epub 2009 Feb 28.

Production and activity of matrix metalloproteinase-9 on the ocular surface increase in dysfunctional tear syndrome

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Production and activity of matrix metalloproteinase-9 on the ocular surface increase in dysfunctional tear syndrome

Suksri Chotikavanich et al. Invest Ophthalmol Vis Sci. 2009 Jul.

Abstract

Purpose: To evaluate production and activity of metalloproteinase (MMP)-9 on the ocular surface of patients with dysfunctional tear syndrome (DTS) and determine any correlation between MMP-9 activity and clinical parameters.

Methods: Forty-six patients with newly diagnosed DTS and 18 control subjects were recruited. Complete ocular surface examinations were performed. Tear MMP-9 activity was assessed with an MMP-9 activity assay in 1 microL of unstimulated tear fluid. Using conjunctival epithelial cells from 19 patients with DTS and 16 controls, levels of MMP-9 and its regulating cytokine mRNA transcripts were evaluated by semiquantitative real-time PCR.

Results: Each of four DTS severity-based groups had significantly higher mean MMP-9 activities than did the control group, which was 8.39 +/- 4.70 ng/mL. The DTS4 group had the highest MMP-9 activity (381.24 +/- 142.83 ng/mL), for which the mean was significantly higher than that of other DTS groups. In addition, patients with DTS had significantly higher levels of IL-1beta, IL-6, TNF-alpha, and TGF-beta1 mRNA transcripts in their conjunctival epithelia than did the control subjects. Tear MMP-9 activities showed significant correlation with symptom severity scores, decreased low-contrast visual acuity, fluorescein tear break-up time, corneal and conjunctival fluorescein staining, topographic surface regularity index (SRI), and percentage area of abnormal superficial corneal epithelia by confocal microscopy.

Conclusions: Tear MMP-9 activity was significantly higher in patients with DTS. This activity was associated with increased mRNA expression of MMP-9 and its regulating genes and correlated strongly with clinical parameters. MMP-9 appears to be a potentially useful biomarker for diagnosing, classifying, and monitoring DTS.

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Figures

Figure 1
Figure 1
Representative confocal images of superficial corneal epithelium of (A) normal control, (B) DTS2, (C) DTS3, and (D) DTS4 subjects. Scale bar, 50 μm.
Figure 2
Figure 2
Relative levels of MMP-9, IL-1β, IL-6, TNF-α, and TGF-β1 mRNA transcripts in conjunctival epithelia obtained from normal subjects (n = 16) and patients with DTS (n = 19). All data (mean ± SD) were compared with the normal control: *P < 0.05; **P < 0.002.
Figure 3
Figure 3
Correlation of tear MMP-9 activity in the study population (n =64) with (A) symptom severity score, P < 0.001; (B) SRI score, P < 0.001; (C) corneal fluorescein staining score, P < 0.001; (D) conjunctival fluorescein staining score, P < 0.001; (E) decrease in low-contrast visual acuity, P = 0.002; and (F) fluorescein TBUT, P < 0.001. r2 = coefficient of determination.

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