Exogenous growth factors induce the production of ganglion cells at the retinal margin.

Neural progenitors at the retinal margin of the post-hatch chicken normally produce amacrine and bipolar cells, but not photoreceptor or ganglion cells. The purpose of this study was to test whether exogenous growth factors influence the types of cells produced by progenitors at the retinal margin. We injected insulin, FGF2 or a combination of insulin and FGF2 into the vitreous chamber of post-hatch chickens. To assay for growth factor-induced changes at the retinal margin, we used in situ hybridization and immunocytochemistry on cryosections. One day after the final injection, we found that insulin alone stimulated the addition of cells to the retinal margin, but this was not further increased when FGF2 was applied with insulin. Insulin alone increased the number of cells in the progenitor zone that expressed neurofilament, and this was further increased when FGF2 was applied with insulin. These neurofilament-expressing cells in the progenitor zone included differentiating neurons that expressed Islet1 or Hu. Four days after the final dose of growth factor, we found that the production of ganglion cells was induced by co-injection of insulin and FGF2, but not by either insulin or FGF2 alone. We conclude that the types of cells produced by progenitors at the retinal margin can be altered by exogenous growth factors and that normally the microenvironment imposes limitations on the types of neurons produced.