Activation of cell survival signals in the goldfish retinal ganglion cells after optic nerve injury.

Generally, nerve injury of adult mammalian CNS neurons leads to a retrograde neuronal degeneration and cell death. The retinal ganglion cells (RGCs) of rat fail to regenerate and become apoptotic after optic nerve injury. In contrast, goldfish RGCs can survive and regrow their axons after injury. Focusing on this different response of RGCs in both species to optic nerve injury, we compared cell death and cell survival signals in the rat and goldfish RGCs after optic nerve injury. In goldfish retina, levels of phospho-Akt (p-Akt) and phospho-Bad (p-Bad) first rapidly increased at 3-5 days after optic nerve injury. Subsequently, levels of Bcl-2 increased and caspase-3 activity decreased at 10 days after nerve injury. In rat retina, levels of p-Akt and p-Bad first rapidly decreased at 1-2 days after optic nerve injury. Subsequently, levels of Bax and caspase-3 activity increased 6 days after optic nerve crush. These changes after optic nerve injury were all morphologically localized only in the RGCs. The data suggest that goldfish RGCs are warranted the cell survival by rapid p-Akt and subsequent Bcl-2 activations during the optic nerve regeneration, whereas rat RGCs are made a progress of the cell death by rapid inactivation of p-Akt and subsequent activation of Bax after optic nerve crush.