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The role of matrix metalloproteinases in infectious corneal ulcers
Celia García-López1, Marina Rodríguez-Calvo-de-Mora2, Davide Borroni3
1Department of Ophthalmology, Hospital Universitario Virgen de las Nieves, Granada, Spain.
Abstract:
During infectious keratitis, the production of collagenolytic and inflammatory substances, along with increased corneal matrix metalloproteinase (MMP) activity, induces the degradation of corneal collagen and may cause postkeratitis complications, such as opacity, thinning, and corneal perforation. MMPs, especially MMP-2 and MMP-9, are overexpressed in infectious keratitis and sustained over time by inflammatory and nonmicrobial mechanisms. The high MMP levels are correlated with excessive corneal destruction in bacterial, herpetic, fungal, and acanthamoeba infections. Nonspecific treatments, such as tetracyclines, particularly doxycycline, or corticosteroids, are used as adjuvants to antimicrobials to alleviate the disproportionate degradation and inflammation of the corneal layers caused by corneal MMPs and decrease the recruitment and infiltration of inflammatory cells. Treatments showing inhibition of specific MMPs (Galardin, ZHAWOC7726), interfering with pro-MMP activation (EDTA, ascorbic acid), or showing anticytokine effect (epigallocatechin-2-gallate, TRAM-34) have been reported. Other treatments show a direct action over corneal collagen structure such as corneal cross-linking or have been associated with reduction of MMP levels such as amniotic membrane grafting. Although the use of these drugs has been shown in studies to be effective in controlling inflammation, especially in experimental ones, robust studies are still needed based on randomized and randomized clinical trials to demonstrate their potential effect as adjuvants in the management of infectious keratitis.
Insights
Infectious keratitis causes corneal damage due to matrix metalloproteinases (MMPs). Treatments targeting MMPs show promise but require robust clinical trials for effective use in managing this condition.
Area of Science:
- Ophthalmology
- Molecular Biology
- Pharmacology
Background:
- Infectious keratitis leads to corneal collagen degradation via collagenolytic and inflammatory substances.
- Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, are significantly upregulated in infectious keratitis, contributing to corneal damage.
- High MMP levels correlate with severe corneal destruction across various infectious agents.
Purpose of the Study:
- To review current and potential therapeutic strategies for infectious keratitis focusing on matrix metalloproteinase (MMP) inhibition and corneal protection.
- To evaluate the efficacy of existing and experimental treatments in managing inflammation and preventing corneal destruction.
Main Methods:
- Review of literature on infectious keratitis and MMP activity.
- Analysis of various therapeutic agents targeting MMPs, their activation, or downstream effects.
- Examination of treatments acting on corneal collagen structure or associated with MMP level reduction.
Main Results:
- Nonspecific treatments like doxycycline and corticosteroids are used as adjuncts to antimicrobials.
- Specific MMP inhibitors, pro-MMP activation inhibitors, and anticytokine agents have been reported.
- Corneal cross-linking and amniotic membrane grafting are other therapeutic approaches discussed.
Conclusions:
- While experimental studies show promise for MMP-targeting treatments in infectious keratitis, robust randomized clinical trials are necessary.
- Further research is needed to establish the efficacy of these agents as adjuvants in clinical management.
- Controlling MMP activity is crucial for preventing post-keratitis complications like opacity and thinning.
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