重组人粒细胞集落刺激因子（G-CSF）对大鼠前部缺血性视神经病变（rAION）模型的神经保护作用。
Neuroprotective effects of recombinant human granulocyte colony-stimulating factor (G-CSF) in a rat model of anterior ischemic optic neuropathy (rAION).
机构信息
Department of Dermatology, Graduate Institute of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Ophthalmology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan; Department of Ophthalmology and Visual Science, Tzu Chi University, Hualien, Taiwan.
出版信息
Exp Eye Res. 2014 Jan;118:109-16. doi: 10.1016/j.exer.2013.11.012. Epub 2013 Dec 5.
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 μv vs. 31 ± 13 μv, p = 0.04). TUNEL assays showed fewer apoptotic cells in the retinal ganglion cell layers of G-CSF 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 anti-inflammation in the optic nerves as evidenced by less infiltration of ED1-povitive cells.
本研究旨在探讨重组人粒细胞集落刺激因子（G-CSF）对大鼠前部缺血性视神经病变（rAION）模型的神经保护作用。通过在 60 只成年雄性 Wistar 大鼠视神经头部静脉内给予 Rose Bengal 激光诱导光激活，诱导前部缺血性视神经病变（rAION）。大鼠立即接受 G-CSF（皮下注射）或磷酸盐缓冲盐水（PBS）连续 5 天。大鼠在梗塞后 4 周处死。使用逆行标记 Fluoro-gold 计数视网膜神经节细胞（RGC）密度。在 4 周时通过闪光视觉诱发电位（FVEP）评估视觉功能。在视神经（ON）标本中进行视网膜切片的 TUNEL 检测和 ED1（巨噬细胞/小胶质细胞标志物）的免疫组织化学染色。G-CSF 治疗组大鼠中央和中周视网膜的 RGC 密度明显高于 PBS 治疗组（中央视网膜的存活率分别为 71.4%对 33.2%；中周视网膜的存活率分别为 61.8%对 22.7%；均 p<0.05）。FVEP 测量显示，G-CSF 治疗组的 p1 波潜伏期和幅度明显优于 PBS 治疗组（潜伏期 120±11 ms 对 142±12 ms，p=0.03；振幅 50±11 μv 对 31±13 μv，p=0.04）。TUNEL 检测显示，G-CSF 治疗组视网膜神经节细胞层中的凋亡细胞较少[2.1±1.0 个/高倍视野（HPF）对 8.0±1.5/HPF；p=0.0001]。此外，G-CSF 治疗组视神经切片中 ED1 阳性细胞数量减少（16±6/HPF 对 35±10/HPF；p=0.016）。总之，G-CSF 在大鼠前部缺血性视神经病变模型中具有神经保护作用，这在结构上通过 RGC 密度和功能上通过 FVEP 得到证明。G-CSF 可能通过抗 RGC 凋亡和视神经内抗炎的双重作用发挥作用，这表现为 ED1 阳性细胞浸润减少。
Zotero 插件