金魚網膜神経節細胞の視神経再生における抗アポトーシス作用について

抄録

Mature neurons in the mammalian CNS fail to regenerate their axons after injury. Unlike mammals, retinal ganglion cells (RGCs) in the goldfish can successfully regrow their axons, whereas RGCs in the mammals become apoptotic following injury. Focusing on this difference between rat and fish after optic nerve injury, we compared both goldfish and rat RGCs after optic nerve crush with respect to cell death and survival signals. Fish RGCs could survive, whereas rat RGCs died gradually after 6 day treatment. The crude enzyme activity of caspase-3 in the rat retina was specifically activated, accompanying the cell death. By contrast, the activity of caspase-3 in the fish retina was reduced during 10-20 day treatment. We further measured levels of anti-apoptotic Bcl-2 and pro-apoptotic Bax proteins in both goldfish and rat retinas after injury by Western blotting analysis. In goldfish, the retinal level of Bcl-2 and p-Akt, an activated form of survival signal significantly increased 10-20 days after injury. Successively, the p-Akt inactivated Bad, an another pro-apoptotic protein. By contrast, in rat the retina level of Bax significantly increased 6 days after injury. The different behaviors of Bcl-2 family proteins and p-Akt in the goldfish and rat retina were morphologically confirmed to be limited to localize the RGCs by immunohistochemical analysis. The opposing properties of fish and rat retinas in cell death and survival signals offer us some clues for solving the mystery of CNS regeneration. [Jpn J Physiol 54 Suppl:S214 (2004)]