Identification of Matrix Metalloproteinase 3 as a Potential Biomarker for Dry Eye Disease.

PURPOSE: This study aimed to investigate matrix metalloproteinase 3 (MMP-3) levels in tears from patients with dry eye disease (DED) and a DED model and analyze the correlations between tear MMP-3 levels and clinical parameters in patients. METHODS: A hyperosmotic-induced DED model was used to assess the expression levels of MMPs. For this, 59 patients with DED (59 eyes) and 21 healthy volunteers (21 eyes) were enrolled in a cross-sectional study. Clinical parameters related to dry eye and tear MMP-3 levels were collected and analyzed. After blocking MMP-3, the DED-related phenotype was measured to evaluate the role of MMP-3 in the DED model. RESULTS: MMP-3 mRNA expression was significantly increased in the DED model in vitro (P = 0.003), and tear MMP-3 levels were significantly elevated in patients with DED (P < 0.001). Moreover, tear MMP-3 levels were positively correlated with the corneal fluorescence staining (CFS) score (P < 0.001) and disease duration (P < 0.001) in patients with DED. A receiver operating characteristic curve analysis revealed a cutoff value of 41.014 ng/mL for the diagnosis of DED, with a sensitivity of 79.7%, a specificity of 85.7%, and an area under the curve of 0.848 (P < 0.001). In the DED model, MMP-3 inhibition significantly alleviated cell apoptosis and inflammation, as well as increased cell viability. CONCLUSIONS: MMP-3 levels were significantly elevated in both the DED model and in the tears of patients with DED. Tear MMP-3 levels correlated with the CFS score and may likely serve as a biomarker for DED. The inhibition of MMP-3 expression attenuated DED-induced cell apoptosis, increased cell viability, and reduced inflammation in vitro. TRANSLATIONAL RELEVANCE: Tear MMP-3 levels were closely associated with the CFS score of patients with DED, and the inhibition of MMP-3 alleviated the DED-related phenotype in vitro, thereby suggesting that MMP-3 is a potential biomarker for DED diagnosis and could aid in the development of therapeutic targets.