FGF-2 Release from the Lens Capsule by MMP-2 Maintains Lens Epithelial Cell Viability

Author:

Tholozan Frederique M.D.1,Gribbon Christopher2,Li Zheng3,Goldberg Martin W.1,Prescott Alan R.4,McKie Norman3,Quinlan Roy A.1

Affiliation:

1. *School of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, United Kingdom;

2. Protein Design Group, Department of Biochemistry, School of Life Sciences, University of Sussex, Falmer, BN1 9QG, United Kingdom; and

3. School of Clinical Medical Sciences (Gerontology), Henry Wellcome Laboratory for Biogerontology Research, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE, United Kingdom;

4. Centre for High Resolution Imaging and Processing, University of Dundee, Dundee DD1 5LE, United Kingdom

Abstract

The lens is an avascular tissue, separated from the aqueous and vitreous humors by its own extracellular matrix, the lens capsule. Here we demonstrate that the lens capsule is a source of essential survival factors for lens epithelial cells. Primary and immortalized lens epithelial cells survive in low levels of serum and are resistant to staurosporine-induced apoptosis when they remain in contact with the lens capsule. Physical contact with the capsule is required for maximal resistance to stress. The lens capsule is also a source of soluble factors including fibroblast growth factor 2 (FGF-2) and perlecan, an extracellular matrix component that enhances FGF-2 activity. Matrix metalloproteinase 2 (MMP-2) inhibition as well as MMP-2 pretreatment of lens capsules greatly reduced the protective effect of the lens capsule, although this could be largely reversed by the addition of either conditioned medium or recombinant FGF-2. These data suggest that FGF-2 release from the lens capsule by MMP-2 is essential to lens epithelial cell viability and survival.

Publisher

American Society for Cell Biology (ASCB)

Subject

Cell Biology,Molecular Biology

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