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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Conjunctiva / enzymology
  • Conjunctiva / pathology
  • Corneal Topography
  • Dry Eye Syndromes / diagnosis
  • Dry Eye Syndromes / enzymology*
  • Epithelial Cells / enzymology
  • Epithelial Cells / pathology
  • Epithelium, Corneal / enzymology
  • Epithelium, Corneal / pathology
  • Female
  • Fluorophotometry
  • Gene Expression Regulation, Enzymologic / physiology
  • Humans
  • Interleukin-1beta / genetics
  • Interleukin-6 / genetics
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Microscopy, Confocal
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tears / chemistry
  • Tears / enzymology*
  • Transforming Growth Factor beta1 / genetics
  • Tumor Necrosis Factor-alpha / genetics
  • Visual Acuity / physiology


  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • RNA, Messenger
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • Matrix Metalloproteinase 9