SUPPRESSION OF FIBROBLAST GROWTH-FACTOR-2 EXPRESSION BY ANTISENSE OLIGONUCLEOTIDES INHIBITS EMBRYONIC CHICK NEURAL RETINA CELL-DIFFERENTIATION AND SURVIVAL IN-VIVO

During retinal differentiation fibroblast growth factor 2 (FGF2) expre ssion increases in retinal neurons following the sequential appearance of the neuronal layers. The function of the developmental increase of endogenous FGF2 in the developing chick retina was investigated by us ing an antisense strategy, using both optic vesicle cultures and in ov o-intravitreal microinjections. The former model allowed us to study t he consequences of FGF2 down-regulation on early ganglion cell differe ntiation, whereas, in the latter model, subsequent development stages and terminal maturation of the retina were studied. FGF2 inhibition re sulted in reduced ganglion cell differentiation, as visualized by the expression of the ganglion cell-specific RA4 and Islet-1 markers in op tic vesicle cultures. Eyes intravitreally injected with the FGF2-speci fic antisense oligonucleotide exhibited profound retinal differentiati on defects: thinning of the ganglion and outer nuclear (photoreceptors ) cell layers and increased cell death in ganglion cell and inner nucl ear layers. These results indicate that the loss of endogenous FGF2 ca nnot be compensated for in the retina and suggest that, although many other sources of FGF exist in the eye, the main role of the increase i n endogenous FGF2 observed during retinal development is to intrinsica lly stimulate neuron differentiation and to protect neurons against ce ll death. (C) 1998 Wiley-Liss, Inc.