SUPPRESSION OF FIBROBLAST GROWTH-FACTOR-1 AND GROWTH-FACTOR-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 neur ons. 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 fun ctions. We have examined the consequences of selectively and independe ntly inhibiting FGF1 or FGF2 expression using antisense oligonucleotid es in embryonic chick retinal cells, differentiating in vitro. Whether FGF1 or FGF2 expression was inhibited the results were the same: a ma rked reduction in neuronal photoreceptor cells differentiation, an inc rease 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 achiev ing 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 stimul ate their differentiation and promote their survival. (C) 1998 Academi c Press.