Abstract
The retinal ganglion cells(RGCs) of adult rat fail to regenerate and become apoptotic cell death after optic nerve injury. On the contrary, fish RGCs can survive and regenerate their axons after injury. In our previous study, we compared rat and goldfish RGCs after optic nerve injury with respect to the cell death and survival signals. A survival signal, Akt and a pro-apoptotic Bad were rapidly phosphorylated 6-8 fold by 3-5 days after goldfish optic nerve injury. Subsequently, an anti-apoptotic Bcl-2 was increased thereby maintaining the optic nerve regeneration. Furthermore, inhibition of the PI3K by wortmannin dose-dependently suppress neurite outgrowth in culture system. On the other hand, Akt and Bad phosphorylation levels in the rat retina were rapidly decreased 2-3 days after optic nerve injury. It is known that insulin-like growth factor I (IGF-I) is an upper stream growth factors of PI3K/Akt pathways and induces differentiation neural retina and inhibits caspase-3-dependent apoptosis in rat retina. In the present study, IGF-I induced neurite outgrowth and the effect was inhibited by wortmannin in the adult rat retina. To determine the link of IGF-I to PI3K/Akt system, we are now in progress to measure the levels of IGF-I in the goldfish and rat retinas before and after optic nerve transection. [Jpn J Physiol 55 Suppl:S169 (2005)]
