MMP9 Is Involved in Glycation End-Products Induced Increase of Retinal Vascular Permeability in Rats and the Therapeutic Effect of Minocycline

Abstract

Purpose: To determine the role of matrix metalloproteinase 9 (MMP9) in advanced glycation end-products (AGEs) induced damage to blood-retinal barrier (BRB) and the therapeutic effects of minocycline, an MMP inhibitor, against the BRB damages. Methods: Forty-eight Sprague Dawley rats were randomly assigned to 3 groups (16/group): A control group treated with bovine serum albumin (BSA), an AGE-BSA treated group, and a group treated with minocycline after AGE-BSA treatment. The retinas of all the animals were collected 2 weeks after treatment, and the levels of MMP9 protein and mRNA were detected by Western blotting, immunohistochemistry, and semi-quantitative RT-PCR. The permeability of retinal vessels was bio-assayed using the Evans Blue method. The correlation between the vessel permeability and the MMP9 protein levels was analyzed. Results: Compared with the BSA control group, the expression of retinal MMP9 mRNA and protein were significantly increased in the AGE-BSA group, and the retinal vascular permeability was also increased in the AGE-BSA group. After the minocycline treatment, the MMP9 expression was decreased sharply and the abnormal vascular permeability was improved. There was a significant correlation between the MMP9 expression and retinal vascular permeability. Conclusion: MMP9 is involved in the AGE-induced retinal damage of vascular permeability, and the abnormal permeability can be partially reversed by treatment with minocycline.