Suppression of fibroblast growth factors 1 and 2 by antisense oligonucleotides in embryonic chick retinal cells in vitro inhibits neuronal differentiation and survival.

As retinal histogenesis proceeds there is a pronounced increase in the expression of fibroblast growth factor (FGF), reaching its maximum in the mature retina and largely in terminal differentiated retinal neurons. Recent in vivo evidence suggests that exogenous FGF functions as a differentiation and survival factor for a wide variety of cell types including CNS neurons and that endogenous FGF may perform similar functions. We have examined the consequences of selectively and independently inhibiting FGF1 or FGF2 expression using antisense oligonucleotides in embryonic chick retinal cells, differentiating in vitro. Whether FGF1 or FGF2 expression was inhibited the results were the same: a marked reduction in neuronal photoreceptor cells differentiation, an increase in programmed cell death, but no effects on cell proliferation. Even although these two related factors promote the same final effect on retinal cells, namely, neuronal differentiation and survival, their normal combined activities or levels appear to be important in achieving this effect. Stimulation with either exogenous FGF1 or FGF2 served to increase endogenous levels of both FGF1 and FGF2 and reversed the effects of antisense blockade of either FGF1 or FGF2. Our data suggest that although other sources of FGF exist within the eye, the function of endogenous FGF in differentiating retinal neurons may be to stimulate their differentiation and promote their survival.