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(Investigative Ophthalmology and Visual Science. 2001;42:1305-1311.)
© 2001 by The Association for Research in Vision and Ophthalmology, Inc.

FGF: An Autocrine Regulator of Human Lens Cell Growth Independent of Added Stimuli

I. Michael Wormstone1, Katia Del Rio–Tsonis2, Gerald McMahon3, Shigeo Tamiya1, Peter D. Davies1,4, Julia M. Marcantonio1 and George Duncan1

1 From the School of Biological Sciences, University of East Anglia, Norwich, United Kingdom; the 2 Department of Zoology, Miami University, Oxford, Ohio; 3 Sugen, Inc., South San Francisco, California; and the 4 Department of Ophthalmology, West Norwich Hospital, United Kingdom.

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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