title: Autocrine protective mechanisms of human granulocyte colony-stimulating factor (G-CSF) on retinal ganglion cells after optic nerve crush.
abstract: 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, Müller 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 transdifferentiation 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 anti-apoptotic effects on RGCs.
authors.affiliation: Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan, ROC.
authors.forename: Shun-Ping
authors.initials: SP
authors.lastname: Huang
authors.affiliation: Department of Dermatology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, ROC.
authors.forename: Kan-Tang
authors.initials: KT
authors.lastname: Fang
authors.affiliation: Department of Dermatology, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan, ROC; Department of Dermatology, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
authors.forename: Chung-Hsing
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Department of Ophthalmology, Far Eastern Memorial Hospital, Banciao District, New Taipei City, Taiwan, ROC; Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan, ROC.
authors.forename: Tzu-Lun
authors.initials: TL
authors.lastname: Huang
authors.affiliation: Institute of Eye Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, ROC.
authors.forename: Yao-Tseng
authors.initials: YT
authors.lastname: Wen
authors.affiliation: Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan, ROC; Institute of Eye Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, ROC. Electronic address: rktasi@tzuchi.com.tw.
authors.forename: Rong-Kung
authors.initials: RK
authors.lastname: Tsai
mesh_terms: D000818:Animals; D017209:Apoptosis; D019898:Autocrine Communication / Q000187:drug effects*; D002452:Cell Count; D002470:Cell Survival / Q000502:physiology; D054338:Cell Transdifferentiation / Q000187:drug effects; D019610:Cytoprotection; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells; D015151:Immunoblotting; D007279:Injections, Subcutaneous; D008297:Male; D009409:Nerve Crush; D020221:Optic Nerve Injuries / Q000517:prevention & control*; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor
keywords: Autocrine; G-CSF receptor; Human granulocyte colony-stimulating factor (G-CSF); Neuroprotection; Optic nerve crush; Retinal ganglion cells