FGF: An autocrine regulator of human lens cell growth independent of addedstimuli

PURPOSE. Posterior capsule opacification (PCO) arises because of a persiste nt growth of lens epithelial cells. Cultured human lens cells residing on t heir native collagen capsule and main tained in serum-free medium actively grow and thus show an intrinsic capacity for regulation. In the present stu dy, 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 i n a 5% CO2 atmosphere at 35 degreesC. On going observations were by phase-c ontrast microscopy. Cellular architecture was examined by fluorescence cyto chemistry. 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 inhibi tion was achieved using the specific antagonist SU5402. RESULTS. Human lens epithelial cells can maintain metabolic activity for mo re 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, FGF R-1 was identified. Inhibition of FGFR-1 caused a significant retardation o f 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 i n the long-term survival and growth of human lens epithelial cells, indepen dent of external stimuli. Inhibition of FGFR-1 by specific synthetic molecu les, such as SU5402, could provide a potential therapeutic approach to reso lving PCO.