Related Experiment Videos
Doxycycline-a role in ocular surface repair.
1Division of Ophthalmology, University of Bristol, Bristol, UK. Val.Smith@bristol.ac.uk
The British Journal of Ophthalmology
|April 20, 2004
Summary
Doxycycline irreversibly inhibits corneal MMP-2 by chelating metal ions, crucial for its therapeutic effect on ocular surface diseases. Its concentration at the ocular surface is key for this chelating property.
Area of Science:
- Ophthalmology
- Cell Biology
- Pharmacology
Background:
- Doxycycline, a broad-spectrum antibiotic, chelates metal ions and is used for ocular surface diseases.
- Its therapeutic benefits are linked to inhibiting matrix metalloproteinase (MMP) activity and synthesis.
Purpose of the Study:
- To investigate doxycycline's role in inhibiting corneal MMPs.
- To assess its contribution to ocular surface repair mechanisms.
Main Methods:
- Corneal cells (epithelial and keratocytes) were cultured and treated with IL-1alpha, LPS, or doxycycline.
- MMP activity, IL-1alpha, and TIMP levels were quantified using zymography, fluorigenic substrates, and ELISA.
- Cell viability and apoptosis markers (caspase-3) were assessed.
Main Results:
- Doxycycline irreversibly inhibited corneal MMP-2 activity, partly dependent on calcium ions.
- Neither IL-1alpha nor LPS affected MMP/TIMP production by corneal cells.
- Doxycycline at 100 micro M caused keratocyte death and epithelial cell detachment, without activating caspase-3.
Conclusions:
- Doxycycline's irreversible inhibition of corneal MMP-2 is due to metal ion chelation.
- Corneal MMP/TIMP production in vitro is not modulated by IL-1alpha, LPS, or doxycycline.
- Doxycycline's therapeutic value in ocular surface diseases likely depends on its ocular surface concentration and chelating properties.