Feng Liang, Puyang Zhen, Chen Hui, Liang Peiji, Troy John B, Liu Xiaorong
Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL 60208, USA.
Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Biomedical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, IL 60208, USA; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
eNeuro. 2017 Jan 17;4(1). doi: 10.1523/ENEURO.0331-16.2016. eCollection 2017 Jan-Feb.
Brain-derived neurotrophic factor (BDNF), a neurotrophin essential for neuron survival and function, plays an important role in neuroprotection during neurodegenerative diseases. In this study, we examined whether a modest increase of retinal BDNF promotes retinal ganglion cell (RGC) survival after acute injury of the optic nerve in mice. We adopted an inducible Cre-recombinase transgenic system to up-regulate BDNF in the mouse retina and then examined RGC survival after optic nerve crush by imaging. We focused on one subtype of RGC with large soma expressing yellow fluorescent protein transgene that accounts for ∼11% of the total SMI-32-positive RGCs. The median survival time of this subgroup of SMI-32 cells was 1 week after nerve injury in control mice but 2 weeks when BDNF was up-regulated. Interestingly, we found that the survival time for RGCs taken as a whole was 2 weeks, suggesting that these large-soma RGCs are especially vulnerable to optic nerve crush injury. We also studied changes in axon number using confocal imaging, confirming first the progressive loss reported previously for wild-type mice and demonstrating that BDNF up-regulation extended axon survival. Together, our results demonstrate that the time course of RGC loss induced by optic nerve injury is type specific and that overexpression of BDNF prolongs the survival of one subgroup of SMI-32-positive RGCs.
脑源性神经营养因子（BDNF）是神经元存活和功能所必需的一种神经营养因子，在神经退行性疾病的神经保护中发挥着重要作用。在本研究中，我们检测了视网膜BDNF适度增加是否能促进小鼠视神经急性损伤后视网膜神经节细胞（RGC）的存活。我们采用诱导型Cre重组酶转基因系统上调小鼠视网膜中的BDNF，然后通过成像检测视神经挤压后RGC的存活情况。我们聚焦于一种胞体较大、表达黄色荧光蛋白转基因的RGC亚型，该亚型约占SMI-32阳性RGC总数的11%。在对照小鼠中，该亚组SMI-32细胞在神经损伤后的中位存活时间为1周，而在BDNF上调时为2周。有趣的是，我们发现作为一个整体的RGC的存活时间为2周，这表明这些胞体较大的RGC对视神经挤压损伤尤其敏感。我们还使用共聚焦成像研究了轴突数量的变化，首先证实了先前报道的野生型小鼠轴突的逐渐丧失，并证明BDNF上调可延长轴突存活时间。总之，我们的结果表明，视神经损伤诱导的RGC丧失的时间进程具有类型特异性，并且BDNF的过表达可延长SMI-32阳性RGC一个亚组的存活时间。
