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MMP-2 AND MMP-9 SECRETION BY RPE IS STIMULATED BY ANGIOGENIC MOLECULES FOUND IN CHOROIDAL NEOVASCULAR MEMBRANES

HOFFMANN, STEPHAN MD*†; HE, SHIKUN MD; EHREN, MARIANNE MD§; RYAN, STEPHEN J. MD; WIEDEMANN, PETER MD; HINTON, DAVID R. MD*¶‡

doi: 10.1097/01.iae.0000238549.74626.33
Original Articles
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Purpose: Matrix metalloproteinases (MMP)-2 and -9 play an important role in the pathogenesis of choroidal neovascularization (CNV). Retinal pigment epithelial cells (RPE) are an important source of MMPs in the outer retinal environment, however little is known about the local factors that modulate MMP secretion in these cells. The purpose of this study was to determine the effects of CNV involved growth factors and the extracellular matrix molecule fibronectin on MMP-2 and -9 secretion by cultured human RPE.

Methods: MMP-2 and -9 secretion was studied using gelatin zymography, Western blot, and ELISA assay of RPE culture supernatants. The effects of stimulating the cells for 36 hours with vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bGFG), tumor necrosis factor-alpha (TNF-α), or fibronectin (FN), all angiogenic factors found in CNV membranes, was determined.

Results: Resting RPE cells secreted MMP-2 but not MMP-9. Stimulation with TNF-α induced secretion of MMP-9 and increased the secretion of MMP-2. MMP-2 secretion was also increased by stimulation with FN and VEGF, but not bFGF.

Conclusion: The results indicated that the angiogenic molecules VEGF, FN, and TNF-α stimulate MMP-2 and -9 secretion from RPE and thus further promote CNV.

The study determines the effects of choroidal neovascularization involved growth factors and the extracellular matrix molecule fibronectin on MMP-2 and MMP-9 secretion by cultured human retinal pigment epithelial cells.

From the ¶Beckman Macular Research Center at the Doheny Eye Institute, Department of *Ophthalmology and ‡Pathology, Keck School of Medicine, University of Southern California, Los Angeles; †University of Leipzig, Eye Hospital, Germany; and §University Hospital Bergmannsheil, Bochum, Germany.

Supported by NIH grants EY01545 and core grant EY03040, The Arnold and Mabel Beckman Foundation, an award to the USC Department of Ophthalmology from Research to Prevent Blindness, Inc., and Junior Grant 783111062001 from the University of Leipzig.

Reprint requests: David R. Hinton, Department of Pathology and Ophthalmology, Keck School of Medicine, 2011 Zonal Ave., HMR209, Los Angeles, CA 90033; e-mail: dhinton@usc.edu.

© The Ophthalmic Communications Society, Inc.