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Matrix metalloproteinase inhibition in corneal ulceration
Dennis E Brooks1, Franck J Ollivier
1Department Clinical Sciences, College of Veterinary Medicine, University of Florida, 2015 SW 16th Avenue, Gainesville, FL 32608, USA. brooksd@mail.vetmed.ufl.edu
Abstract:
The primary objective of current treatment strategies for infectious keratitis is to sterilize the ulcer as rapidly as possible with topically administered antibiotics. Ulcerative processes can proceed in some cases, despite the absence of microbes, as a result of remaining corneal and tear film MMPs. Combining antibiotic therapy with MMP inhibitors can speed corneal healing, because MMPs play an important role in corneal ulceration and stromal liquefaction. MMPs from the rabbit, horse, and human being are inhibited by metal-binding agents EDTA, NAC, and doxycycline as well as by the serum antiprotease alpha2-macroglobulin. It is not yet certain which proteinase inhibitor has the most favorable therapeutic index for clinical use, although we prefer serum because of its effects on multiple types of proteinases. The MMP inhibitors do have significant therapeutic promise in the treatment of corneal ulceration.
Insights
Infectious keratitis treatment can be improved by combining antibiotics with matrix metalloproteinase (MMP) inhibitors. These inhibitors, like serum, reduce corneal ulceration and speed healing, offering therapeutic promise.
Area of Science:
- Ophthalmology
- Corneal Disease Research
- Wound Healing
Background:
- Current infectious keratitis treatments focus on rapid antibiotic sterilization.
- Corneal ulceration can persist post-microbial eradication due to matrix metalloproteinases (MMPs).
- MMPs contribute significantly to corneal ulceration and stromal liquefaction.
Purpose of the Study:
- To investigate the potential of combining antibiotic therapy with MMP inhibitors for enhanced corneal healing.
- To evaluate the efficacy of various MMP inhibitors in treating infectious keratitis.
Main Methods:
- Assessing the role of MMPs in persistent ulcerative processes.
- Testing the inhibitory effects of metal-binding agents (EDTA, NAC, doxycycline) and serum antiprotease (alpha2-macroglobulin) on MMPs from rabbit, horse, and human corneas.
- Comparing the therapeutic potential of different proteinase inhibitors.
Main Results:
- MMPs were identified as key factors in post-antibiotic corneal ulceration.
- EDTA, NAC, doxycycline, and alpha2-macroglobulin demonstrated MMP inhibitory activity.
- Serum showed promise due to its broad-spectrum proteinase inhibition.
Conclusions:
- Combining antibiotic therapy with MMP inhibitors shows significant therapeutic promise for infectious keratitis.
- MMP inhibitors can accelerate corneal healing by mitigating ulceration and stromal liquefaction.
- Further research is needed to determine the optimal proteinase inhibitor for clinical application.
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