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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- 作者：Chung-Hsing Chang ; Tzu-Lun Huang ; Shun-Ping Huang ; Rong-Kung Tsai
- 关键词：rat anterior ischemic optic neuropathy ; rAION ; granulocyte colony stimulating factor ; neuroprotection ; retinal ganglion cells
- 刊名：Experimental Eye Research
- 出版年：January, 2014
- 年：2014
- 卷：118
- 期：Complete
- 页码：109-116
- 全文大小：1324 K
文摘
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聽<聽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聽卤聽11聽ms vs. 142聽卤聽12聽ms, p聽=聽0.03; amplitude 50聽卤聽11聽渭v vs. 31聽卤聽13聽渭v, p聽=聽0.04). TUNEL assays showed fewer apoptotic cells in the retinal ganglion cell layers of G-CSF treated rats [2.1聽卤聽1.0 cells/high power field (HPF) vs. 8.0聽卤聽1.5/HPF; p聽=聽0.0001]. In addition, the number of ED1 positive cells was attenuated at the optic nerve sections of G-CSF-treated rats (16聽卤聽6/HPF vs. 35聽卤聽10/HPF; p聽=聽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.