Production and activity of matrix metalloproteinase-9 on the ocular surface increase in dysfunctional tear syndrome.
OBJECTIVE
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.
Chotikavanich
Suksri
S
Department of Ophthalmology, Ocular Surface Center, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas 77030, USA.
de Paiva
Cintia S
CS
Li
De Quan
de Q
Chen
Joseph J
JJ
Bian
Fang
F
Farley
William J
WJ
Pflugfelder
Stephen C
SC
D000328:Adult; D003228:Conjunctiva / Q000201:enzymology / Q000473:pathology; D019781:Corneal Topography; D015352:Dry Eye Syndromes / Q000175:diagnosis / Q000201:enzymology*; D004847:Epithelial Cells / Q000201:enzymology / Q000473:pathology; D019573:Epithelium, Corneal / Q000201:enzymology / Q000473:pathology; D005260:Female; D015590:Fluorophotometry; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013666:Tears / Q000737:chemistry / Q000201:enzymology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014792:Visual Acuity / Q000502:physiology
C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9