FGF-2 release from the lens capsule by MMP-2 maintains lens epithelial cell viability.
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.
Tholozan
Frederique M D
FM
School of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, United Kingdom.
Gribbon
Christopher
C
Li
Zheng
Z
Goldberg
Martin W
MW
Prescott
Alan R
AR
McKie
Norman
N
Quinlan
Roy A
RA
D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016895:Culture Media, Serum-Free; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007903:Lens Capsule, Crystalline / Q000166:cytology* / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D008854:Microscopy, Electron; D012995:Solubility; D019311:Staurosporine / Q000494:pharmacology
D051017:Apoptosis Regulatory Proteins; D016895:Culture Media, Serum-Free; D016222:Fibroblast Growth Factor 2; D020778:Matrix Metalloproteinase 2; D019311:Staurosporine
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