July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
The therapeutic effects of Pegylated granulocyte-colony-stimulating factor (PEG-GCSF) in a rat model of anterior ischemic optic neuropathy (rAION)
Author Affiliations & Notes
  • Rong-Kung Tsai
    Institute of Eye Research, Tzu-Chi Medical Center, Hualien, Taiwan
    Institute of Medical Sciences, Tzu Chi Univesity, Hualien, Taiwan
  • Yao-Tseng Wen
    Institute of Eye Research, Tzu-Chi Medical Center, Hualien, Taiwan
  • Footnotes
    Commercial Relationships   Rong-Kung Tsai, None; Yao-Tseng Wen, None
  • Footnotes
    Support  Research Grant from Tzu Chi General Hospital
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3349. doi:
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      Rong-Kung Tsai, Yao-Tseng Wen; The therapeutic effects of Pegylated granulocyte-colony-stimulating factor (PEG-GCSF) in a rat model of anterior ischemic optic neuropathy (rAION). Invest. Ophthalmol. Vis. Sci. 2018;59(9):3349.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Granulocyte-colony-stimulating factor (G-CSF), an old drug, has been widely used in patients with chemotherapy-induced leucopenia and stem cells mobilization in bone marrow transplantation. Our previous reports demonstrated that systemic applications of G-CSF provides good neuro-protective effects in rat models of anterior ischemic optic neuropathy (rAION). The administration of G-CSF, subcutaneous injection once daily for 5 days, may bring leucocytosis side effect. The half-life of G-CSF is short about 3.5 hours. Pegylated granulocyte colony stimulating factor (PEG-GCSF; Neulasta) has a much longer half-life, reducing the necessity of consecutive daily injections. Therefore, the purpose of this study is to evaluate the therapeutic effects of one shot of intravitreal injection with PEG-G-CSF the rAION model.

Methods : The therapeutic window of PEG-GCSF was determined by measuring Flash-VEP and RGC density. The anti-apoptotic effect was measured by using TUNEL assay. The ON inflammation was evaluated by IHC of ED1 staining. Macrophage/microglia polarization was evaluated by using real time RT-PCR analysis.

Results : The amplitudes of P1-N2 in Flash-VEP and the survival rate of RGCs in the PEG-GCSF-treated group (before 2 days post-infract) were significantly higher than that of the PBS-treated group (p<0.05). The numbers apoptotic RGCs in the PEG-GCSF-treated groups (before 2 days post-infarct) were 2.0- and 1.9-fold lower than that of the PBS-treated group (p=0.013, p=0.013). Macrophage infiltration was reduced by 2.96- and 1.79-fold by PEG-GCSF treatment starting on day 0 and 1 post-rAION induction, respectively, compared with PBS treatment (p<0.05). Treatment with PEG-GCSF also increases the expression of M2 macrophage and inhibits the expression of M1 macrophage in the ON.

Conclusions : One shot of intravitreal injection of PEG-GCSF before 2 days post-rAION has neuroprotective effects in a rAION model. This treatment preserved better visual function in flash VEP as well as RGC morphometry. In addition, intravitreal injection of PEG-GCSF before2 days post-infract also prevented the macrophage infiltration and subsequent inflammation to the ON.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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