Autocrine protective mechanisms of human granulocyte colony stimulating factor (G-CSF) on retinal ganglion cells after optic nerve crush

被引:9
作者
Huang, Shun-Ping [1 ]
Fang, Kan-Tang [2 ]
Chang, Chung-Hsing [3 ,4 ]
Huang, Tzu-Lun [5 ,6 ]
Wen, Yao-Tseng [7 ]
Tsai, Rong-Kung [6 ,7 ]
机构
[1] Tzu Chi Univ, Dept Mol Biol & Human Genet, Hualien 97002, Taiwan
[2] Buddhist Tzu Chi Gen Hosp, Dept Dermatol, Hualien, Taiwan
[3] Kaohsiung Med Univ, Chung Ho Mem Hosp, Dept Dermatol, Kaohsiung, Taiwan
[4] Kaohsiung Med Univ, Dept Dermatol, Kaohsiung, Taiwan
[5] Far Eastern Mem Hosp, Dept Ophthalmol, New Taipei, Taiwan
[6] Tzu Chi Univ, Inst Med Sci, Hualien 97002, Taiwan
[7] Buddhist Tzu Chi Gen Hosp, Eye Res Inst, Hualien, Taiwan
关键词
Human granulocyte colony-stimulating factor (G-CSF); Autocrine; Retinal ganglion cells; G-CSF receptor; Optic nerve crush; Neuroprotection; FOCAL CEREBRAL-ISCHEMIA; PERIPHERAL-BLOOD; SKELETAL-MUSCLE; STEM-CELLS; RATS; NEUROGENESIS; RECEPTOR; NEURONS; MODEL; MICE;
D O I
10.1016/j.exer.2015.10.010
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
This study investigated the role of autocrine mechanisms in the anti-apoptotic effects of human granulocyte colony-stimulating factor (G-CSF) on retinal ganglion cells (RGCs) after optic nerve (ON) crush. We observed that both G-CSF and G-CSF receptor (G-CSFR) are expressed in normal rat retina. Further dual immunofluorescence staining showed G-CSFR immunoreactive cells were colocalized with RGCs, Muller cells, horizontal and amacrine cells. These results confirm that G-CSF is an endogenous ligand in the retina. The semi-quantitative RT-PCR finding demonstrated the transcription levels of G-CSF and G-CSFR were up-regulated after ON crush injury. G-CSF treatment further increased and prolonged the expression level of G-CSFR in the retina. G-CSF has been shown to enhance transdifferentiation of the mobilized hematopoietic stem cells into tissue to repair central nervous system injury. We test the hypothesis that the hematopoietic stem cells recruited by G-CSF treatment can transdifferentiate into RGCs after ON crush by performing sublethal irradiation of the rats 5 days before ON crush. The flow cytometric analysis showed the number of CD34 positive cells in the peripheral blood is significantly lower in the irradiated, crushed and G-CSF-treated group than the sham control group or crush and G-CSF treated group. Nevertheless, the G-CSF treatment enhances the RGC survival after sublethal irradiation and ON crush injury. These data indicate that G-CSF seems unlikely to induce hematopoietic stem cell trans differentiation into RGCs after ON crush injury. In conclusion, G-CSF may serve an endogenous protective signaling in the retina through direct activation of intrinsic G-CSF receptors and downstream signaling pathways to rescue RGCs after ON crush injury, exogenous G-CSF administration can enhance the antiapoptotic effects on RGCs. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码:132 / 140
页数:9
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