以neuritin为靶点修复大鼠视神经损伤的作用及机制

项目名称： 以neuritin为靶点修复大鼠视神经损伤的作用及机制

项目编号： No.31271282

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 许家军

作者单位： 中国人民解放军第二军医大学

项目金额： 70万元

中文摘要： RGC内在再生能力低下是视神经伤后难再生的关键。最近研究表明找准靶点增强RGC内在再生能力，受损视神经能持续、活跃地再生。Neuritin是众多NTF发挥神经营养作用的关键和共同下游因子，为介导雄激素和电刺激促进神经再生的必须和关键分子，在视觉系统高表达，提示其为影响RGC内在再生能力的关键NTF。我们预试验发现视神经伤后早期的视神经和视网膜中Neuritin表达均显著下调。未见用Neuritin治疗视神经损伤的研究报道。本课题拟首先研究大鼠视神经压榨伤后视觉系统Neuritin基因表达的时空变化；伤后即玻璃体注射Neuritin或Neuritin基因重组慢病毒，用视网膜体外培养、形态学、分子生物学和功能检测等方法，观察视神经再生、RGC存活、基因表达和功能恢复等，结合对体外受损RGC5的相应研究，研究Neuritin修复视神经伤的作用及机制，为治疗视神经及中枢神经伤提供新手段和理论依据。

中文关键词： 视神经；损伤；neuritin；基因治疗；机制

英文摘要： Low intrinsic regeneration ability of RGC is critical for optic nerve difficult to regenerate. Recent reports suggest that enhancing intrinsic regeneration ability of RGC by targeting to special molecules induce sustained and robust regeneration in the injured optic neve of mouse. Neuritin is a crucial, commom downstream molecule through which NTF play their neurotrophic role. It is also a necessary, crucial molecule through which testosterone and electrical stimulation potentiate nerve regeneration. The expression of neuritin is abundant in the visual nervous system, which imply that neuritin may be a crucial NTF in regulating intrinsic regeneration ability of RGC. Our previous study indicated that neuritin be significantly down-regulated in the optic neve and retina during early phase after rat optic neve injury. It is so far not reported that neuritin is given to treat optic nerve injury. We will display the changes of spatial and temporal expression patterns in the visual nervous system after crush of rat optic nerve. Then, vitreal injection of neuritin or neuritin adeno-associated viral vector will immediately be performed after optic nerve to increase neuritin content in the visual nervous system. To explore effects of the targeting neuritin on repairing the injured rat optic nerve and their mechanisms, re

英文关键词： optic nerve；injury；neuritin；gene therapy；mechanism