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Serum Matrix Metalloproteinase Levels and Activities in Patients With Glaucoma

¹ Ophthalmology Discovery, Pharmacia Corp., St Louis, MO, United States
² Discovery Oncology, Pharmacia Corp., St Louis, MO, United States
³ Arthritis and Inflammation, Pharmacia Corp., St Louis, MO, United States
⁴ Ophthalmology Discovery & Dept. of Ophthalmology, Pharmacia Corp.& Washington University, St Louis, MO, United States

Commercial Relationships: J. Yang, None; K. Zhang, None; C.P. Howard, None; D.L. Knoerzer, None; C.F. Voliva, None; D.J. Welsch, None; M.B. Wax, None.

Abstract

Purpose: We previously reported higher expression of matrix metalloproteinases (MMP-1, MMP-2 and MMP-3) in optic nerve heads from post-mortem glaucoma patients compared to age-matched normal controls. To further confirm the possible role of MMPs in the pathogenesis of glaucoma we assayed the levels and activities of MMPs in sera from glaucoma patients and corresponding age-matched controls.
Methods: This study included 48 glaucoma patients (25 normal pressure glaucoma NPG; 23 primary open angle glaucoma POAG) and 21 age-matched controls. Selected MMPs (MMP-1, MMP-7, MMP-8, MMP-9) and TIMP-1 in the sera were assayed by ELISA. The composite MMP enzymatic activities in the sera were measured using a proprietary fluorescence peptide assay (FPA) that is efficiently cleaved by MMP-2, MMP-8, MMP-9, MMP-13 and MMP-14 but not by MMP-1, MMP-3 or MMP-7.
Results: The levels of MMP-1, MMP-7, MMP-8 and TIMP-1 in the sera were similar between glaucoma patients and controls, but total MMP-9 (zymogen and active species) was decreased in the POAG group, compared with age-matched controls and the NPG group (t-test, p<0.01, and p<0.001 respectively). No difference was observed between control and POAG group. However, statistically significant increased MMP activities were observed in the NPG group by FPA assay, compared with the age-matched controls and the POAG group (t-test, p<0.01; p<0.05). There was no difference between POAG and age-matched controls (t-test, p>0.05).
Conclusions: POAG patients appear to have decreased MMP-9 serum levels compared to age-matched controls, whereas increased MMP enzymatic activity was observed in the NPG patients. These results suggest that MMPs may have a role in the initiation and/or sustainment of glaucomatous optic neuropathy in some patients.

Keywords: enzymes/enzyme inhibitors • clinical research methodology

© 2003, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any part of this abstract, contact the ARVO Office at arvo{at}arvo.org.