Fibroblast growth factor (FGF) induces different responses in lens epithelial cells depending on its concentration

We reported previously that epithelial cells in expiants from neonatal rat lenses, when cultured in the presence of fibroblast growth factor (FGF), showed increased proliferation, cell migration and fibre differentiation; moreover, fibre differentiation in response to the basic form of FGF (bFGF) was virtually completely blocked by an anti-bFGF antibody. In the present study, we report a detailed analysis of the effects of bFGF on cells in the central region of lens epithelial explants. Proliferation in explants was assessed by measuring [³H]thymi-dine incorporation. Cell migration was measured by labelling cells in explants with fluorescein isothiocyanate (FITC)-dextran and monitoring them by UV fluorescence microscopy. Fibre differentiation in explants was assessed on the basis of β-crystallin accumulation. This study showed that half maximal activities for the three responses, proliferation, migration and fibre differentiation, were achieved at different concentrations of bFGF, namely, 0·15, 3 and 40 ng ml^-1, respectively. Thus, the response of lens epithelial cells to bFGF varied qualitatively, as well as quantitatively, as the concentration increased. Monitoring FITC-dextran injected cells for up to 5 days after exposure to bFGF allowed analysis of the interrelation between various responses to bFGF in individual cells. As expected some cells divided in response to FGF, mainly within the first three days. However, whether or not they divided, all labelled cells responded to FGF by migrating and elongating. Maximal migration occurred during the first day of culture and maximal elongation was achieved by day 4. It was also found that [³H]thymidine incorporation and cell migration were substantially inhibited (90–93 %) by the anti-bFGF antibody shown previously to inhibit fi-crystallin accumulation, providing strong support for the conclusion that FGF is the molecule responsible for inducing all three responses. All these findings lead us to suggest that variations in FGF concentration in the different ocular media may be involved in controlling and maintaining lens polarity and lens growth patterns.