A new study has identified matrix metalloproteinase-3 (MMP-3) as a promising biomarker and therapeutic target for dry eye disease (DED), according to researchers from the Eye & ENT Hospital of Fudan University.

Findings

In a cross-sectional study of 80 participants (59 DED patients and 21 healthy controls) recently published in Translational Vision Science & Technology, the researchers observed significantly elevated levels of MMP-3 in the tears of DED patients. Median tear MMP-3 concentrations rose from 32.96 ng/mL in controls to 51.99 ng/mL in affected patients (P<.001). In one severe case, the concentration exceeded 300 ng/mL.

Tear MMP-3 levels were found to positively correlate with 2 clinical indicators: corneal fluorescein staining (CFS) score (P=.041) and diseaseduration (P=.038). Receiver operating characteristic analysis showed that a tear MMP-3 cutoff value of 42.014 ng/mL provided a sensitivity of 79.7% and a specificity of 85.7% for diagnosing DED (area under the curve = 0.848, P<.001).

Using a hyperosmolarity-induced human corneal epithelial cell model of DED, the research team also found that:

• MMP-3 mRNA expression increased more than 40-fold under hyperosmotic conditions. MMP-1 and MMP-9 were also upregulated, but to a lesser degree

• Inflammatory cytokines (eg, TNF-α, IL-6, IL-8) were significantly elevated

• Treatment with 6 nM MMP-3 inhibitor significantly reduced inflammation, improved cell viability, and lowered apoptosis rates. Treatment with 4 nM MMP-3 inhibitor significantly reduced MMP-3 expression.

“These findings suggest a potential temporal hierarchy in MMP activation during dry eye pathogenesis, mirroring patterns observed in other inflammatory conditions,” the authors wrote.

Methods

“MMPs are notable for their ability to remodel the extracellular matrix and play a role in cell signaling, immune regulation, and wound healing,” the authors explained. “MMPs can destroy tight junctions in the ocular surface epithelium, thereby affecting barrier function.” They added that, in addition to MMP-3, MMP-9, and MMP-1 (collagenases), MMP-2 (gelatinases), and MMP-7 (matrilysin) have also been implicated in DED.

Patients in the study were 18 to 85 years old and were diagnosed with DED if they met 3 of 4 criteria:

1. ocular surface disease index (OSDI) of at least 13

2. tear film breakup time (BUT) of up to 10 seconds

3. Schirmer Ⅰ test (SⅠT) up to 10 mm/5 minutes

4. CFS score of at least 1

Controls were included if they had OSDI less than 12, tear film BUT of more than 10 seconds, SIT of more than 10 mm/5 minutes, and CFS score of less than 1. If patients had binocular DED, only the right eye was included.

Patients were excluded if they had a history of eye disease (e.g., deformity, active inflammation, infection, glaucoma, or uveitis); had undergone ocular surgery, trauma, and treatment; wore contact lenses within the last 6 months; and had a history of treatment with topical anti-inflammatories within the last 3 months before the study.

Study limitations included a modest sample size, volume limitations in tear samples, and potential recall bias in patient-reported disease duration. The researchers recommended multicenter studies with larger cohorts, broader biomarker panels (eg, MMP-9, TNF-α), longitudinal designs, and standardized autoimmune disease classification to confirm these results and explore clinical applications.

As MMP-3 levels are studied further, the authors concluded, future therapeutic targets could emerge: “Our findings not only provide a novel target for DED diagnosis and foundational research, but also lay the groundwork for translating MMP-3 from bench to bedside, thus offering a promising avenue for future clinical applications.”