Production and Activity of Matrix Metalloproteinase-9 on the Ocular Surface Increase in Dysfunctional Tear Syndrome

• Published in: Investigative ophthalmology & visual science Vol. 50; no. 7; pp. 3203 - 3209
• Main Authors: Chotikavanich, Suksri, de Paiva, Cintia S, Li, De Quan, Chen, Joseph J, Bian, Fang, Farley, William J, Pflugfelder, Stephen C
• Format: Journal Article
• Language: English
• Published: Rockville, MD ARVO 01.07.2009; Association for Research in Vision and Ophtalmology
• Subjects: Adult; Biological and medical sciences; 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; Eye and associated structures. Visual pathways and centers. Vision; Female; Fluorophotometry; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Enzymologic - physiology; Humans; Interleukin-1beta - genetics; Interleukin-6 - genetics; Male; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Medical sciences; Microscopy, Confocal; Ophthalmology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Tears - chemistry; Tears - enzymology; Transforming Growth Factor beta1 - genetics; Tumor Necrosis Factor-alpha - genetics; Vertebrates: nervous system and sense organs; Visual Acuity - physiology; Ocular; Enzyme; Tear; Metalloendopeptidases; Activity; Increase; Gelatinase B; Surface; Eye; Peptidases; Production; Hydrolases; Ophthalmology
• ISSN: 0146-0404; 1552-5783; 1552-5783
• DOI: 10.1167/iovs.08-2476

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. 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. 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. 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.