Matrix metalloproteinases and their inhibitors in aqueous humor of patients with pseudoexfoliation syndrome/glaucoma and primary open-angle glaucoma.

Abstract

To determine the presence, activity, and quantitative differences of matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in aqueous humor and serum samples of patients with pseudoexfoliation (PEX) syndrome, PEX glaucoma (PEXG), primary open-angle glaucoma (POAG), and cataract. Aqueous humor and serum samples were collected from 100 patients with PEX syndrome, PEX glaucoma (PEXG), POAG, and cataract, respectively. Levels of MMP-1, -2, -3, -7, -9, and -12 and TIMP-1 and -2 were determined by zymography, Western blot analysis, and specific immunoassays. Activity assay kits were used to quantitate levels of endogenously activated MMP-2 and -9. MMP-2, -3, -7, -9, and -12 and TIMP-1 and -2 were identified in human aqueous humor samples from all groups of patients with a six to sevenfold molar excess of TIMPs over MMPs. Whereas serum samples showed no significant differences, total MMP-2 and -3 and TIMP-1 and -2 were detected at significantly higher concentrations in aqueous samples from PEX eyes with and without glaucoma compared with cataractous eyes. MMP-2 and -3 and TIMP-1 were also detected in higher, but not significantly different, amounts in aqueous samples of POAG eyes. However, levels of endogenously activated MMP-2 were significantly decreased in both PEX and POAG samples. The ratio of MMP-2 to its principal inhibitor TIMP-2 was balanced in cataract samples, but was decreased in samples from patients with PEXG, resulting in an excess of TIMP-2 over MMP-2. The findings suggest that complex changes in the local MMP-TIMP balance and reduced MMP activity in aqueous humor may promote the abnormal matrix accumulation characteristic of PEX syndrome and may be causally involved in the pathogenesis of both PEX glaucoma and POAG.