Neuroprotective Effect of Rapamycin in Optic Nerve Transection Model

ABSTRACT

PURPOSE: The present study investigated whether rapamycin activated autophagy in retinal ganglion cells (RGC) and evaluated its effect on RGC survival following optic nerve transection (ONT). METHODS: The activation of autophagy in RGCs after intravitreal injection of rapamycin was evaluated with the immunohistochemical staining of phospho-S6 ribosomal protein. Rapamycin or 0.1% DMSO was injected intravitreally immediately after ONT. At 1 and 2 weeks after ONT, the RGCs were counted. Rapamycin and autophagy inhibitors, 3-methyladenine or Wortmannin were co-injected intravitreally after ONT and the RGCs were counted 1 week later. RESULTS: Expression of phospho-S6 ribosomal protein was decreased in RGCs after intravitreal injection of rapamycin. The RGC number was significantly higher in the rapamycin group than in the control group 1 week after ONT. However, the RGC number was not different between the 2 groups 2 weeks after ONT. Repeated intravitreal injection of rapamycin at 1-week intervals showed neuroprotection 2 weeks after ONT. The RGC number was not different between the control group and the co-injection group of rapamycin-autophagy inhibitor. CONCLUSIONS: Activated autophagy by rapamycin was neuroprotective in RGC after ONT.