Purchase this article with an account.
J. L. Jacot, T. A. Jacot, S. Hahto, J. Helis, C. J. Sheppard, J. D. Sheppard, Jr., F. A. Lattanzio, Jr., P. B. Williams; Azithromycin Alters ProMMP-2 and TIMP-1 Following Corneal Wounding in an Experimental Animal Model of Diabetic Ocular Complications. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2663.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To determine the effect of topical azithromycin (AzaSite®) and its vehicle (DuraSite®) on MMP-2 and TIMP-1 in tears of control and galactosemic rats. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), which modulate activity of certain MMPs, are involved in multiple processes in damaged and diseased eyes. MMP-2 is elevated after corneal wounding, ulceration, erosion, collagen remodeling and repair.
Male SD rats were randomized into 4 groups (n=6/group) and fed ad lib chow with either 50% starch (control) or 50% D-galactose. The dietary groups were treated bilaterally either with 3x/day 1% AzaSite®or DuraSite® for two months. Tears were collected 2 weeks after induction of a sterile 3 mm central corneal epithelial wound under anesthesia. Tears were placed in Tris (pH 7.4) w/ protease inhibitors. MMP-2 in tears was evaluated by gelatin sepharose affinity precipitation followed by gelatin zymography. Samples were normalized by equal protein load and semi-quantified using NIH-imageJ for integrated density units/per area. Microbead antibody immunoassay was used to determine tear levels of TIMP-1 (ng/ml).
Tears from galactosemic rats exhibited elevated proMMP-2 relative to control group. Compared to DuraSite® treated galactosemic rats, the AzaSite® treatment suppressed proMMP-2 levels by 38%. Control group showed a 17% decrease in proMMP-2 with AzaSite® compared to DuraSite®. There was a trend towards elevation of TIMP-1 levels in the AzaSite® treated galactosemic rats compared to DuraSite®. No appreciable trend was observed in the control group.
This study on modulation of tear levels of MMP-2 and TIMP-1 by the antibiotic, AzaSite®, provides preliminary mechanistic data for the use of AzaSite® therapy in the management of ocular surface tissue remodeling/injury, diabetic and neurotrophic keratopathies where corneal MMP levels can be elevated.
This PDF is available to Subscribers Only