Neuroprotective effects of recombinant human granulocyte colony-stimulating factor (G-CSF) in a rat model of anterior ischemic optic neuropathy (rAION).

Abstract

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.

• Authors: Chung-Hsing Chang, Tzu-Lun Huang, Shun-Ping Huang, Rong-Kung Tsai
• Journal: Experimental eye research (Exp Eye Res) Vol. 118 Pg. 109-16 (Jan 2014) ISSN: 1096-0007 [Electronic] England
• PMID: 24316388 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Recombinant Proteins
• Granulocyte Colony-Stimulating Factor

Topics

• Animals
• Apoptosis (drug effects)
• Disease Models, Animal
• Evoked Potentials, Visual (drug effects)
• Granulocyte Colony-Stimulating Factor (pharmacology)
• Immunohistochemistry
• In Situ Nick-End Labeling
• Male
• Optic Nerve (drug effects, pathology, physiopathology)
• Optic Neuropathy, Ischemic (drug therapy, pathology, physiopathology)
• Rats
• Rats, Wistar
• Recombinant Proteins (pharmacology)
• Retinal Ganglion Cells (drug effects, pathology)