OVEREXPRESSION OF FGF-2 MODULATES FIBER CELL-DIFFERENTIATION AND SURVIVAL IN THE MOUSE LENS

During mammalian embryogenesis, the ocular lens forms through a tempor ally and spatially regulated pattern of differentiation which is thoug ht to be coordinated at least in part by the FGF-1 and FGF-2 members o f the fibroblast growth factor (FGF) family. Previous transgenic exper iments in which FGF-1 or dominant negative FGF receptors were overexpr essed in the lens indicated that FGF-1 could induce differentiation wh ile differentiated lens cells rely upon FGF signaling for their surviv al, In this study, we asked if the 17.5 kDa FGF-2 protein was capable of inducing differentiation of lens cells in transgenic mice, Unexpect edly, differentiation was inhibited by lens-specific expression of a t ransgene encoding a secreted form of the 17.5 kDa bovine FGF-2 protein under the transcriptional control of the murine aii-crystallin promot er (alpha AIgFGF-2 transgenic mice), To address the possibility that F GF-2 functions as a modulator of fiber cell survival, alpha AIgFGF-2 t ransgenic mice were crossed to transgenic mice exhibiting extensive ap optosis in the lens due to the functional inactivation of the retinobl astoma protein (alpha AE7 transgenic mice), The level of apoptosis in the lenses of double transgenic mice was substantially reduced as comp ared to the level in lenses from alpha AE7 only mice, These studies in dicate that FGF-2 can act as a modulator of the later stages of differ entiation including fiber cell survival. Additionally, they imply that control of lens development by FGFs is a complex process in which FGF -1 and FGF-2 play distinct roles.