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

Chang, Chia-Wen; Huang, Tzu-Lun; Huang, Shangyu; Tsai, Rong‐Kung

doi:10.1016/j.exer.2013.11.012

Cited by 37 publications

(59 citation statements)

References 37 publications

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“…Inflammation might be responsible for certain ON damage that occurs in NAION (Hayreh and Zimmerman, 2008; Salgado et al, 2011). In a rat model of anterior ischemic optic neuropathy (rAION), breakdown of the blood–ON barrier was found to occur within hours post-induction of infarct (Bernstein and Miller, 2015), followed by the early recruitment of extrinsic macrophages and activation of resident microglia at the core of the ischemic ON (Slater et al, 2008; Bernstein et al, 2011; Chang et al, 2014; Huang et al, 2015). Activated macrophages have been reported to improve neuronal survival through the secretion of oncomodulin, and to play a key role in phagocytosis and in the removal of myelin debris (soluble Nogo) to enhance remyelination and axon regeneration after ischemic axonal degeneration (Yin et al, 2003; Selvaraju et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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

Wen

Huang

et al. 2016

Disease Models &Amp; Mechanisms

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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<0.05). This was compatible with 3.3- and 1.7-fold reductions in ON vascular permeability after G-CSF treatment compared with PBS treatment (P<0.05). Microglial activation was increased by 3.8- and 3.2-fold in the early (beginning treatment at day 0 or 1) G-CSF-treated group compared with the PBS-treated group (P<0.05). Immediate (within 30 mins of infarct) treatment with G-CSF also induced M2 microglia/macrophage activation. The cytokine levels were lower in the group that received immediate G-CSF treatment compared to those in the later G-CSF treatment group (P<0.05). Early treatment with G-CSF stabilized the blood–ON barrier to reduce macrophage infiltration and induced M2 microglia/macrophage polarization to decrease the expressions of pro-inflammatory cytokines in this rAION model.

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Section: Introductionmentioning

confidence: 99%

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

Wen

Huang

et al. 2016

Disease Models &Amp; Mechanisms

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“…16 Briefly, after general anesthesia, Rose Bengal (RB; Sigma-Aldrich Corp., St. Louis, MO, USA) was administered intravenously through the tail vein using a 28-gauge needle (2.5 mM RB in PBS/1 mL/kg animal weight). The sham laser treatment consisted of illuminating the ON region with an argon laser without RB.…”

Section: Raion Inductionmentioning

confidence: 99%

“…16,25,28 Briefly, we used a visual electrodiagnostic system (UTAS-E3000, LKC Technologies, Gaithersburg, MD, USA) to measure the FVEP. To exclude the possibility that the contralateral fellow eye contaminated the FVEP test, we covered the fellow eye while performing the stimulation.…”

Section: Raion Inductionmentioning

confidence: 99%

Early Methylprednisolone Treatment Can Stabilize the Blood-Optic Nerve Barrier in a Rat Model of Anterior Ischemic Optic Neuropathy (rAION)

Huang

Wen

Chang

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…However, others have shown that an argon green laser and indirect ophthalmoscope also produce rAION. 50 Laser applications were consistent and repeatable. The spot size completely covered the optic nerve, and the presence of Rose Bengal dye was reliably observed during the laser application (i.e., a yellow glow was detected within the vasculature of the optic nerve during laser delivery).…”

Section: Methods Utilized In Raion Experimentsmentioning

confidence: 99%

Progesterone Treatment in Two Rat Models of Ocular Ischemia

Allen

Olsen

Sayeed

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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Citation: Allen RS, Olsen TW, Sayeed I, et al. Progesterone treatment in two rat models of ocular ischemia. Invest Ophthalmol Vis Sci. 2015;56:2880-2891. DOI:10.1167/iovs.14-16070 PURPOSE. To determine whether the neurosteroid progesterone, shown to have protective effects in animal models of traumatic brain injury, stroke, and spinal cord injury, is also protective in ocular ischemia animal models.METHODS. Progesterone treatment was tested in two ocular ischemia models in rats: a rodent anterior ischemic optic neuropathy (rAION) model, which induces permanent monocular optic nerve stroke, and the middle cerebral artery occlusion (MCAO) model, which causes transient ischemia in both the retina and brain due to an intraluminal filament that blocks the ophthalmic and middle cerebral arteries. Visual function and retinal histology were assessed to determine whether progesterone attenuated retinal injury in these models. Additionally, behavioral testing and 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining in brains were used to compare progesterone's neuroprotective effects in both retina and brain using the MCAO model. RESULTS.Progesterone treatment showed no effect on visual evoked potential (VEP) reduction and retinal ganglion cell loss in the permanent rAION model. In the transient MCAO model, progesterone treatment reduced (1) electroretinogram (ERG) deficits, (2) MCAO-induced upregulation of glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP), and (3) retinal ganglion cell loss. As expected, progesterone treatment also had significant protective effects in behavioral tests and a reduction in infarct size in the brain. CONCLUSIONS.Progesterone treatment showed protective effects in the retina following MCAO but not rAION injury, which may result from mechanistic differences with injury type and the therapeutic action of progesterone.

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

Cited by 37 publications

References 37 publications

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

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

Early Methylprednisolone Treatment Can Stabilize the Blood-Optic Nerve Barrier in a Rat Model of Anterior Ischemic Optic Neuropathy (rAION)

Progesterone Treatment in Two Rat Models of Ocular Ischemia

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