Effects of neurotrophins on embryonic retinal outgrowth

The neurotrophins brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3) and neurotrophin 4 (NT-4), as well as their receptors, are expressed in both the developing and adult visual system. In vitro and in vivo studies suggest that BDNF in particular can enhance the survival of developing and injured retinal ganglion cells. We have previously shown that BDNF secreted by transgenic fibroblasts promotes outgrowth from embryonic retinae when cotransplanted into the cerebral cortex. The roles of NT-3 and NT-4 were investigated in this system along with BDNF, on retinal neuronal outgrowth, both on in vivo retinal transplants and on in vitro retinal explant cultures. Our results confirm that BDNF promotes retinal outgrowth of embryonic retinae both in vivo, and in vitro. NT4 was shown only to promote retinal outgrowth in vitro in the presence of proliferating glia. NT-3 was shown to have no effect on embryonic retinal outgrowth in vivo or in vitro. While other molecules have been proposed to play a role, the present results, together with evidence for BDNF in the developing superior colliculus and receptors on retinal cells, argue for an important role for BDNF in normal retinal neuronal outgrowth, with NT-4 playing a secondary role.