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Originally published as MBC in Press, 10.1091/mbc.E06-05-0416 on August 15, 2007

Vol. 18, Issue 11, 4222-4231, November 2007

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

Frederique M.D. Tholozan*, Christopher Gribbon{dagger}, Zheng Li{ddagger}, Martin W. Goldberg*, Alan R. Prescott§, Norman McKie{ddagger}, and Roy A. Quinlan*

*School of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, United Kingdom; {ddagger}School of Clinical Medical Sciences (Gerontology), Henry Wellcome Laboratory for Biogerontology Research, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE, United Kingdom; {dagger}Protein Design Group, Department of Biochemistry, School of Life Sciences, University of Sussex, Falmer, BN1 9QG, United Kingdom; and §Centre for High Resolution Imaging and Processing, University of Dundee, Dundee DD1 5LE, United Kingdom

Submitted May 15, 2006; Revised July 24, 2007; Accepted August 8, 2007
Monitoring Editor: M. Bishr Omary

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.

This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-05-0416) on August 15, 2007.

Formula The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Roy Quinlan (r.a.quinlan{at}dur.ac.uk).




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