시신경절단모델에서 라파마이신의 신경보호효과에 대한 연구

Neuroprotective Effect of Rapamycin in Optic Nerve Transection Model

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. J Korean Ophthalmol Soc 2012;53(8):1150-1156