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Published on: May 2, 2020
In vivo characterization of doxycycline effects on tear metalloproteinases in patients with chronic blepharitis
Alfonso Iovieno1, Alessandro Lambiase, Alessandra Micera
1Interdisciplinary Center for Biomedical Research (CIR), Laboratory of Ophthalmology, University of Roma Campus Bio-Medico, Roma - Italy.
Purpose:
Matrix metalloproteinases (MMPs) have a role in the pathogenesis of rosacea-associated chronic blepharitis. Doxycycline is largely used as a treatment for recalcitrant chronic blepharitis. It has been shown in vitro that doxycycline inhibits MMPs activation. The aim of this study was to investigate in vivo the effect of doxycycline in modulating MMPs in patients with chronic idiopathic blepharitis.
Methods:
Eight patients (6 male, 2 female; mean age 45.7+/-17.5 years) were included in the study. Doxycycline (100 mg) was administered orally, twice a day, for 2 weeks and once a day for an additional 2 weeks. Clinical signs and symptoms were evaluated and scored (0-3) at baseline and after 4 weeks. Total sign (TSS) and total symptom (TSyS) scores were calculated. Tear samples and conjunctival impression cytologies were collected at baseline and after 4 weeks of treatment to evaluate MMP-9 and TIMP-1 expression and activity.
Results:
An improvement in TSS (4.5+/-1.1 vs 2.7+/-1.5) and TSyS (6.6+/-1.3 vs. 3.1+/-1.9) was observed after 4 weeks, with significant amelioration of hyperemia, marginal blepharitis, and superficial punctuate keratopathy. Zymography revealed a decrease of MMP-9 activity after 4 weeks. MMP-9 mRNA and protein levels did not change, while an upregulation of TIMP-1 expression was observed.
Conclusions:
This study suggests that 4-week treatment with doxycycline significantly improved symptoms and signs in patients with chronic blepharitis in association with a decrease in MMP-9 activity. Upregulation of TIMP-1 is proposed as a possible mechanism of MMP-9 inactivation.
Insights
Doxycycline treatment for chronic blepharitis reduced matrix metalloproteinase-9 (MMP-9) activity and improved patient symptoms and signs. This suggests doxycycline
Area of Science:
- Ophthalmology
- Dermatology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of rosacea-associated chronic blepharitis.
- Doxycycline is a common treatment for recalcitrant chronic blepharitis, with known in vitro MMP inhibitory effects.
Purpose of the Study:
- To investigate the in vivo effect of doxycycline on matrix metalloproteinases (MMPs) in patients with chronic idiopathic blepharitis.
Main Methods:
- Eight patients with chronic idiopathic blepharitis received oral doxycycline (100 mg twice daily for 2 weeks, then once daily for 2 weeks).
- Clinical signs and symptoms were assessed using Total Sign Score (TSS) and Total Symptom Score (TSyS) at baseline and after 4 weeks.
- Tear and conjunctival samples were analyzed for MMP-9 and TIMP-1 expression and activity using zymography and other methods.
Main Results:
- A significant improvement in TSS and TSyS was observed after 4 weeks of doxycycline treatment.
- Clinical improvements included reduced hyperemia, marginal blepharitis, and superficial punctate keratopathy.
- Zymography showed decreased MMP-9 activity, while MMP-9 mRNA and protein levels remained unchanged; TIMP-1 expression was upregulated.
Conclusions:
- Four-week doxycycline treatment significantly improved signs and symptoms in chronic blepharitis patients, correlating with reduced MMP-9 activity.
- Upregulation of TIMP-1 is proposed as a potential mechanism for MMP-9 inactivation by doxycycline.
