title: 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: Department of Dermatology, Graduate Institute of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Chung-Hsing
authors: CH
authors: Chang
authors: Department of Ophthalmology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan; Department of Ophthalmology and Visual Science, Tzu Chi University, Hualien, Taiwan.
authors: Tzu-Lun
authors: TL
authors: Huang
authors: Department of Ophthalmology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan; Department of Medical Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan; Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan.
authors: Shun-Ping
authors: SP
authors: Huang
authors: Department of Ophthalmology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan; Department of Ophthalmology and Visual Science, Tzu Chi University, Hualien, Taiwan; Department of Ophthalmology, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: rktsai@tzuchi.com.tw.
authors: Rong-Kung
authors: RK
authors: Tsai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D005074:Evoked Potentials, Visual / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009900:Optic Nerve / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D018917:Optic Neuropathy, Ischemic / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor
keywords: granulocyte colony stimulating factor; neuroprotection; rAION; rat anterior ischemic optic neuropathy; retinal ganglion cells