中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2012, Vol. 7 ›› Issue (10): 725-730.

• 原著:视神经损伤修复保护与再生 •    下一篇

Dose-dependent and combined effects of N-methyl- D-aspartate receptor antagonist MK-801 and nitric oxide synthase inhibitor nitro-L-arginine on the survival of retinal ganglion cells in adult hamsters

  

  • 收稿日期:2012-01-15 修回日期:2012-03-30 出版日期:2012-04-05 发布日期:2012-04-05

Dose-dependent and combined effects of N-methyl- D-aspartate receptor antagonist MK-801 and nitric oxide synthase inhibitor nitro-L-arginine on the survival of retinal ganglion cells in adult hamsters

Yaoyu Li1, An’an Yang2, Tingting Zhu1, Zhao Liu2, Siwei You2, Kwok-Fai So3   

  1. 1 Department of Ophthalmology, General Hospital of Beijing Military Region, Beijing 100700, China
    2 Institute of Neurosciences, the Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
    3 Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
  • Received:2012-01-15 Revised:2012-03-30 Online:2012-04-05 Published:2012-04-05
  • Contact: Siwei You, Professor, Doctoral supervisor, Institute of Neurosciences, the Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China; Kwok-Fai So, Ph.D., Chair professor, Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China yousiwei@fmmu.edu.cn;hrmaskf@hkucc.hku.hk
  • About author:Yaoyu Li☆, Ph.D., Professor, Department of Ophthalmology, General Hospital of Beijing Military Region, Beijing 100700, China Yaoyu Li and An’an Yang contributed equally to this work.

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Abstract:

This study investigated the effects of daily intraperitoneal injections of N-methyl-D-aspartate receptor antagonist MK-801 and nitric oxide synthase inhibitor nitro-L-arginine (L-NA) on the survival of retinal ganglion cells (RGCs) at 1 and 2 weeks after unilateral optic nerve transection in adult hamsters. The left optic nerves of all animals were transected intraorbitally 1 mm from the optic disc and RGCs were retrogradely labeled with Fluorogold before they received different daily dosages of single MK-801 or L-NA as well as daily combinational treatments of these two chemicals. All experimental and control animals survived for 1 or 2 weeks after optic nerve transection. Our results revealed that the mean numbers of surviving RGCs increased and then decreased when the dosage of MK-801 (1.0, 3.0 and 4.5 mg/kg) and L-NA (1.5, 3.0, 4.5 and 6.0 mg/kg) increased at both 1 and 2 weeks survival time points. Daily combinational use of 1.0 mg/kg MK-801 and 1.5 mg/kg L-NA lead to a highest RGC number that was even higher than the sum of the RGC numbers in 1.0 mg/kg MK-801 and 1.5 mg/kg L-NA subgroups at 2 weeks. These findings indicated that both MK-801 and L-NA can protect axotomized RGCs in a dose-dependent manner and combinational treatment of these chemicals possesses a potentiative and protective effect.

Key words: retinal ganglion cells, optic nerve transection, N-methyl-D-aspartate receptor, nitric oxide synthase, neuronal survival, hamster