Matrix metalloproteinases and their tissue inhibitors in aqueous humor of patients with primary open-angle glaucoma, exfoliation syndrome, and exfoliation glaucoma.
Objective: 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.
Methods: 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.
Results: 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).
Conclusions: 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.