Early applications of granulocyte colony-stimulating factor (G-CSF) can stabilize the blood-optic-nerve barrier and ameliorate inflammation in a rat model of anterior ischemic optic neuropathy (rAION)

• Published in: Disease models & mechanisms 2016-10, Vol.9 (10), p.1193-1202
• Main Authors: Wen, Yao-Tseng, Huang, Tzu-Lun, Huang, Sung-Ping, Chang, Chung-Hsing, Tsai, Rong-Kung
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Biomarkers - metabolism; Blood–optic-nerve barrier; Capillary Permeability - drug effects; Cell Survival - drug effects; Disease Models, Animal; Edema; Evoked Potentials, Visual - drug effects; Granulocyte colony-stimulating factor (G-CSF); Granulocyte Colony-Stimulating Factor - pharmacology; Granulocyte Colony-Stimulating Factor - therapeutic use; Granulocytes; Immunohistochemistry; Inflammation; Inflammation - blood; Inflammation - pathology; Inflammation Mediators - metabolism; Interleukin-1beta - metabolism; Macrophage infiltration; Macrophages - drug effects; Macrophages - metabolism; Male; Microglia - drug effects; Microglia - metabolism; Microglia/macrophage polarization; Optic Nerve - drug effects; Optic Nerve - pathology; Optic Neuropathy, Ischemic - blood; Optic Neuropathy, Ischemic - drug therapy; Optic Neuropathy, Ischemic - pathology; Rat anterior ischemic optic neuropathy (rAION); Rats, Wistar; Retinal Ganglion Cells - drug effects; Retinal Ganglion Cells - metabolism; Retinal Ganglion Cells - pathology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1754-8403; 1754-8411
• DOI: 10.1242/dmm.025999

Granulocyte colony-stimulating factor (G-CSF) was reported to have a neuroprotective effect in a rat model of anterior ischemic optic neuropathy (rAION model). However, the therapeutic window and anti-inflammatory effects of G-CSF in a rAION model have yet to be elucidated. Thus, this study aimed to determine the therapeutic window of G-CSF and investigate the mechanisms of G-CSF via regulation of optic nerve (ON) inflammation in a rAION model. Rats were treated with G-CSF on day 0, 1, 2 or 7 post-rAION induction for 5 consecutive days, and a control group were treated with phosphate-buffered saline (PBS). Visual function was assessed by flash visual evoked potentials at 4 weeks post-rAION induction. The survival rate and apoptosis of retinal ganglion cells were determined by FluoroGold labeling and TUNEL assay, respectively. ON inflammation was evaluated by staining of ED1 and Iba1, and ON vascular permeability was determined by Evans Blue extravasation. The type of macrophage polarization was evaluated using quantitative real-time PCR (qRT-PCR). The protein levels of TNF-α and IL-1β were analyzed by western blotting. A therapeutic window during which G-CSF could rescue visual function and retinal ganglion cell survival was demonstrated at day 0 and day 1 post-infarct. Macrophage infiltration was reduced by 3.1- and 1.6-fold by G-CSF treatment starting on day 0 and 1 post-rAION induction, respectively, compared with the PBS-treated group (P