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I. Michael Wormstone, Katia Del Rio–Tsonis, Gerald McMahon, Shigeo Tamiya, Peter D. Davies, Julia M. Marcantonio, George Duncan; FGF: An Autocrine Regulator of Human Lens Cell Growth Independent of Added Stimuli. Invest. Ophthalmol. Vis. Sci. 2001;42(6):1305-1311.
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purpose. Posterior capsule opacification (PCO) arises because of a persistent
growth of lens epithelial cells. Cultured human lens cells residing on
their native collagen capsule and maintained in serum-free medium
actively grow and thus show an intrinsic capacity for regulation. In
the present study, the authors investigated the role of the putative
FGF autocrine system in human capsular bags.
methods. Capsular bags were prepared from human donor eyes and maintained in a
5% CO2 atmosphere at 35°C. On-going observations were by
phase-contrast microscopy. Cellular architecture was examined by
fluorescence cytochemistry. De novo protein synthesis was determined by
the incorporation of 35S-methionine. Basic fibroblast growth factor
(FGF) and FGF receptor (R)-1 were detected using enzyme-linked
immunosorbent assay (ELISA) and reverse transcription–polymerase chain
reaction (RT-PCR) techniques. FGFR-1 inhibition was achieved using the
specific antagonist SU5402.
results. Human lens epithelial cells can maintain metabolic activity for more
than 1 year in a protein-free medium. Basic FGF was shown to be present
in capsular bags throughout culture and also in capsular bags removed
from donor eyes that had previously undergone cataract surgery.
Furthermore, FGFR-1 was identified. Inhibition of FGFR-1 caused a
significant retardation of growth on the posterior capsule. On no
occasion did any treated bag reach confluence, whereas all match-paired
control samples did.
conclusions. The results provide evidence that FGF plays an integral role in the
long-term survival and growth of human lens epithelial cells,
independent of external stimuli. Inhibition of FGFR-1 by specific
synthetic molecules, such as SU5402, could provide a potential
therapeutic approach to resolving PCO.
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