IGF enhancement of FGF-induced fibre differentiation and DNA synthesis in lens explants

The aim of this study was to carry out an analysis of the effects of insulin-like growth factors (IGFs) on responses induced by FGF in lens epithelial explants. Central explants from postnatal rats were cultured with concentrations of FGF-2 known to stimulate fibre differentiation or cell proliferation, with and without IGF-I or IGF-II at concentrations ranging from 0-1000 ng ml(-1). Fibre-specific beta- and gamma-crystallin accumulation was determined by ELISA after 5-10 days culture and [H-3]thymidine incorporation was assessed at 18-24 hr. Generally, both FGF and IGF were added on day 0. In the absence of FGF, IGF induced significant DNA synthesis, but negligible fibre differentiation. When included with FGF, however, IGF synergistically enhanced both DNA synthesis and the accumulation of fibre-specific crystallins. For beta-crystallin, it was shown that this enhancement reflected a substantial increase in the amount of crystallin in individual cells, not merely an increase in cell numbers. The potentiating effects of IGF-I and IGF-II were comparable. For the fibre differentiation response, it was shown that the cells remained responsive to the synergistic influence of IGF-1 for up to 4 days of culture. The dose response characteristics of the fibre differentiation response suggest that mediation occurs mainly through the IGF-I receptor. Because IGF, as well as FGF, is known to be present in the ocular media, IGF may have a role in modulating FGF-induced responses In the lens in vivo. (C) 1996 Academic Press Limited