Neuroprotective effects of recombinant human granulocyte colony-stimulating factor (G-CSF) in neurodegeneration after optic nerve crush in rats

作者：Tsai Rong Kung^*; Chang Chung Hsing; Wang Hwei Zu

来源：Experimental Eye Research, 2008, 87(3): 242-250.

DOI：10.1016/j.exer.2008.06.004

• granulocyte colony-stimulating factor
• rat model
• optic nerve crush
• ocular neuroprotection
• flash visual-evoked potential
• RGC density

The purpose of the present study was to investigate the effects of granulocyte colony-stimulating factor (G-CSF) on neurodegeneration of optic nerve (ON) and retinal ganglion cells (RGCs) in a rat model of ON crush. The ONs of adult male Wistar rats (150-180g) were crushed by a standardized method. The control eyes received a sham operation. G-CSF (100 mu g/kg/day in 0.2 ml phosphate-buffered saline) or phosphate-buffered saline (PBS control) was immediately administered after ON crush for 5 days by subcutaneous injection. Rats were euthanized at 1 or 2 weeks after the crush injury. RGC density was counted by retrograde labeling with FluoroGold application to the superior colliculus, and visual function was assessed by flash visual evoked potentials (FVEP). TUNEL assay, Western blot analysis and immunohistochemistry of p-AKT in the retina and ED1 (marker of macrophage/microglia) in the ON were conducted. 2 weeks after the insult, the RGC densities in the central and mid-peripheral retinas in ON-crushed, G-CSF-treated rats were significantly higher than that of the corresponding ON-crushed, PBS-treated rats (survival rate was 60% vs. 19.6% in the central retina; 46.5% vs. 23.9% in mid-peripheral retina, respectively; p < 0.001). FVEP measurements showed a significantly better preserved latency of the p1 wave in the ON-crushed, G-CSF-treated rats than the ON-crushed, PBS-treated rats (78 +/- 9 ms in the sham operation group, 98 +/- 16 ms in the G-CSF-treated group, and 174 +/- 16 ms in the PBS-treated group; In < 0.001). TUNEL assays showed fewer apoptotic cells in the retinal sections in the ON-crushed, G-CSF-treated rats. p-AKT immunoreactivity Was Up-regulated in the retinas of the ON-crushed, G-CSF-treated rats at 1 and 2 weeks. In addition, the number of ED1-positive cells was attenuated at the lesion site of the optic nerve in the ON-crushed, G-CSF-treated group. From these results, we gather that administration of G-CSF is neuroprotective in the rat model of optic nerve crush, as demonstrated both structurally by RGC density and functionally by FVEP. G-CSF may work by being anti-apoptotic involving the p-AKT signaling pathway as well as by attenuation of the inflammatory responses at the injury site, as evidenced by less ED1-positive cell infiltration in the optic nerve.

• 出版日期2008-9
• 单位河北医科大学