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J. L. Jacot, T. A. Jacot, J. D. Sheppard, Jr., F. A. Lattanzio, P. B. Williams, K. Brubaker; Evaluation of MMP2/9 Modulation by Azithromycin and DuraSite on Human Corneal Epithelial Cells and Bovine Corneal Endothelial Cells in vitro. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1985.
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© ARVO (1962-2015); The Authors (2016-present)
Matrix metalloproteinases (MMPs) coordinate multiple processes in normal, damaged, and diseased corneas. In normal corneas, MMP-9 is expressed in epithelium and affects epithelial regeneration and integrity of the basement membrane. Over-expression of MMP-9 involves degradation of epithelial basement membrane and contributes to failure of re-epitheliazation following injury, these elements can lead to repair defects and ulceration. MMP-9 slows cellular replication and delays inflammatory responses. MMP-2 is expressed predominantly in stromal fibroblasts and endothelium, sub-serving a surveillance function. MMP-2 is elevated after wounding, collagen remodeling, and stromal repair. The objective of the present study was to determine the MMP modulatory effect of azithromycin (AzaSiteTM) and its vehicle (DuraSite) on human corneal epithelial cells (HCEC) and bovine corneal endothelial cells (BCEC) in vitro.
Primary cultures of HCEC and BCEC were established and exposed overnight (19 to 24 hrs) to serum-free media containing 50 uM of AzaSite, equivalent volume of the vehicle DuraSite, or serum-free media only (untreated control). Assessment of cell morphology was conducted pre- and post drug treatment. The amount of MMP 2/9 secreted by these cultured cells in the presence of AzaSite, vehicle, or serum-free media was evaluated by gelatin zymography normalized by equal protein load. Zymogram results were quantified using MetaMorph software for relative area measurements. Data are expressed as a percent of the area obtained from the untreated control group.
Cultured human corneal epithelial cells secret abundant pro-MMP-9 and pro-MMP-2. AzaSite treatment suppressed pro-MMP-9 levels by 33% of the untreated control group, and showed a suppressive effect greater than vehicle treatment. The bovine corneal endothelial cells secreted predominantly pro-MMP-2. AzaSite and DuraSite had no apparent effect on pro-MMP-2 levels in epithelial or endothelial cells.
This in vitro study on corneal MMP-9 selective modulation by the antibiotic AzaSite provides preliminary data for exploring the use of AzaSite for the management of corneal wound healing in clinical conditions where corneal MMP levels are elevated such as in diabetic keratopathy, dry eye, and following keratectomy.
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