Matrix Metalloproteinases and Their Tissue Inhibitors in Aqueous Humor of Patients With Primary Open-Angle Glaucoma, Exfoliation Syndrome, and Exfoliation Glaucoma

Abstract

To study extracellular matrix (ECM) metabolism by matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in aqueous humor (AH) samples collected from primary open-angle glaucoma (POAG), exfoliation syndrome (EXS), and exfoliation glaucoma (EXG) in relation to samples derived from cataract control patients. Seventy-one AH samples were collected during cataract extraction and trabeculectomy. The expression and molecular forms of MMP-2, -8, -9, -13, and -14 and tissue inhibitor of metalloproteinases-1 and -2 (TIMPs) were analyzed by Western immunoblotting. Gelatinase and collagenase activities were studied by zymography and type I collagen degradation assays, respectively. MMP-2 and TIMP-2 concentrations were measured by ELISA assays. By Western immunoblotting all the studied MMPs were mainly in their latent form in all diagnostic groups. Zymography demonstrated that MMP-2 represents the major gelatinase in AH. Similarly, type I collagenolytic activity was low and similar in cataract and glaucoma samples. In ELISA measurements the TIMP-2 levels were significantly elevated in glaucoma and EXS samples in comparison to cataract controls (P < 0.05). TIMP-2 is elevated in glaucomatous process over MMP-2, which support and further extend the conjuncture that the ECM accumulation rather than degradation predominates in the pathogenesis of POAG and EXG.