Neuroprotective Effect of Rapamycin in Optic Nerve Transection Model. |
Seok Hwan Kim, Young Keun Han, Ki Ho Park, Yoo Jung Kim |
1Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea. eye129@paran.com 2Department of Ophthalmology, SMG - SNU Boramae Medical Center, Seoul, Korea. 3Department of Ophthalmology, Seoul National University Hospital, Seoul, Korea. 4Seoul National University Clinical Research Institute, Seoul, Korea. |
시신경절단모델에서 라파마이신의 신경보호효과에 대한 연구 |
김석환1,2⋅한영근1,2⋅박기호1,3⋅김유정4 |
Department of Ophthalmology, Seoul National University College of Medicine1, Seoul, Korea Department of Ophthalmology, SMG - SNU Boramae Medical Center2, Seoul, Korea Department of Ophthalmology, Seoul National University Hospital3, Seoul, Korea Seoul National University Clinical Research Institute4, Seoul, Korea |
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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. |
Key Words:
Autophagy;Neuroprotection;Optic nerve transaction;Rapamycin;Retinal ganglion cells |
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