Neuroprotective effects of recombinant human granulocyte colony-stimulating factor (G-CSF) in a rat model of anterior ischemic optic neuropathy (rAION)
Neuroprotective effects of recombinant human granulocyte colony-stimulating factor (G-CSF) in a rat model of anterior ischemic optic neuropathy (rAION)
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DOI：
10.1016/j.exer.2013.11.012
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发表时间：
2014-01-01
影响因子：
3.4
通讯作者：
Tsai, Rong-Kung
中科院分区：
文献类型：
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作者：
Chang, Chung-Hsing;Huang, Tzu-Lun;Tsai, Rong-Kung
本研究的目的是研究重组人粒细胞集落刺激因子（G-CSF）在大鼠前缺血性视神经病变（rAION）模型中的神经保护作用。采用激光诱导光激活60只成年雄性Wistar大鼠视神经头静脉注射孟加拉玫瑰，诱导前路缺血性视神经病变（rAION）。大鼠立即皮下注射G-CSF（皮下注射）或磷酸缓冲盐水（PBS）连续5天。梗塞后4周对大鼠实施安乐死。用氟金逆行标记法计数视网膜神经节细胞（RGCs）密度。4周时用闪烁视觉诱发电位（FVEP）评估视觉功能。在视神经（ON）标本中进行视网膜切片TUNEL检测和巨噬细胞/小胶质细胞标志物ED1免疫组化染色。G-CSF处理大鼠中央视网膜和中周视网膜RGC密度显著高于pbs处理大鼠（中央视网膜存活率为71.4%比33.2%，中周视网膜存活率为61.8%比22.7%,p < 0.05）。FVEP测量显示，与pbs处理的大鼠相比，g - csf处理的大鼠p1波的潜伏期和振幅保存明显更好（潜伏期120 +/- 11 ms vs. 142 +/- 12 ms, p = 0.03；振幅50 +/- 11 pv vs. 31 +/- 13 pv, p = 0.04）。TUNEL实验显示，GCSF处理大鼠视网膜神经节细胞层中凋亡细胞较少[2.1 +/- 1.0个细胞/高倍视野（HPF） vs. 8.0 +/- 1.5个细胞/高倍视野；P = 0.0001]。此外，g - csf处理大鼠视神经切片ED1阳性细胞数量减少（16 6/HPF vs. 35 +/- 10/HPF; p = 0.016）。综上所述，G-CSF在大鼠前缺血性视神经病变模型中具有神经保护作用，从结构上通过RGC密度和功能上通过FVEP证实了这一点。G-CSF可能通过抗凋亡和抗视神经炎症的双重作用来促进RGC存活，ed1阳性细胞的浸润较少。(C) 2013 Elsevier Ltd.版权所有。
The purpose of this study was to investigate the neuroprotective effects of recombinant human granulocyte colony stimulating factor (G-CSF), as administered in a rat model of anterior ischemic optic neuropathy (rAION). Using laser-induced photoactivation of intravenously administered Rose Bengal in the optic nerve head of 60 adult male Wistar rats, an anterior ischemic optic neuropathy (rAION) was inducted. Rats either immediately received G-CSF (subcutaneous injections) or phosphate buffered saline (PBS) for 5 consecutive days. Rats were euthanized at 4 weeks post infarct. Density of retinal ganglion cells (RGCs) was counted using retrograde labeling of Fluoro-gold. Visual function was assessed by flash visual-evoked potentials (FVEP) at 4 weeks. TUNEL assay in the retinal sections and immunohistochemical staining of ED1 (marker of macrophage/microglia) were investigated in the optic nerve (ON) specimens. The RGC densities in the central and mid-peripheral retinas in the G-CSF treated rats were significantly higher than those of the PBS-treated rats (survival rate was 71.4% vs. 33.2% in the central retina; 61.8% vs. 22.7% in the mid-peripheral retina, respectively; both p < 0.05). FVEP measurements showed a significantly better preserved latency and amplitude of the p1 wave in the G-CSF-treated rats than that of the PBS-treated rats (latency120 +/- 11 ms vs. 142 +/- 12 ms, p = 0.03; amplitude 50 +/- 11 p.v vs. 31 +/- 13 pv, p = 0.04). TUNEL assays showed fewer apoptotic cells in the retinal ganglion cell layers of GCSF treated rats [2.1 +/- 1.0 cells/high power field (HPF) vs. 8.0 +/- 1.5/HPF; p = 0.0001]. In addition, the number of ED1 positive cells was attenuated at the optic nerve sections of G-CSF-treated rats (16 6/HPF vs. 35 +/- 10/HPF; p = 0.016). In conclusion, administration of G-CSF is neuroprotective in the rat model of anterior ischemic optic neuropathy, as demonstrated both structurally by RGC density and functionally by FVEP. G-CSF may work via the dual actions of anti-apoptosis for RGC surviving as well as antiinflammation in the optic nerves as evidenced by less infiltration of ED1-povitive cells. (C) 2013 Elsevier Ltd. All rights reserved.