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Therapeutic Retrobulbar Inhibition of STAT3 Protects Ischemic Retina Ganglion Cells
Wong, Mansin1; Li, Ying1; Li, Shang2; Zhang, Shaodan1,3; Li, Weiyi1,4; Zhang, Pei1; Chen, Chaoran5; Barnstable, Colin J.6; Zhang, Samuel S.6; Zhang, Chun1; Huang, Ping1,7
关键词Optic Nerve Head Astrocyte Astrogliosis Jak/stat3 Pathway Neuroprotection Glaucoma
刊名MOLECULAR NEUROBIOLOGY
2015-12-01
DOI10.1007/s12035-014-8945-9
52期:3页:1364-1377
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Neurosciences
研究领域[WOS]Neurosciences & Neurology
关键词[WOS]OPTIC-NERVE HEAD ; INTRAOCULAR-PRESSURE ELEVATION ; SPINAL-CORD-INJURY ; GROWTH-FACTOR ; RAT MODEL ; EXPERIMENTAL GLAUCOMA ; REACTIVE ASTROCYTES ; CEREBRAL-ISCHEMIA ; AXONAL-TRANSPORT ; JAK/STAT PATHWAY
英文摘要

Astrocytes play an important role in the pathogenesis of glaucoma. Abnormal activation and/or proliferation of astrocytes, termed astrogliosis, have been observed during optic nerve degeneration. Our previous study identified signal transducer and activator of transcription 3 (STAT3) signaling as an important regulator of astrogliosis in the optic nerve in a rat transient ischemia/reperfusion model. In this study, we used pharmacological inhibition of STAT3 activation in the same model to assess whether it could attenuate reactive astrogliosis and to observe its influence on optic nerve damage and retinal ganglion cell (RGC) damage. Our findings show that retrobulbar inhibition of STAT3 in optic nerve head astrocytes leads to (a) increased nerve fiber bundle survival in the optic nerve, (b) increased nerve fiber bundle and RGC survival in the retina, (c) decreased astrocyte reactivation in the optic nerve (d) decreased remodeling of astrocytes in the optic nerve, and (e) no influence of astrocyte reactivation inside the retina. Taken together, the Janus kinase/STAT3 pathway contributes to astrocyte reactivation in the optic nerve, which plays a pivotal role in neurodegeneration after transient ischemia/reperfusion in vivo. Inhibition of this pathway provides a potential therapeutic strategy for the treatment of glaucomatous neuropathy, and could extend to other neurodegenerative diseases.

语种英语
WOS记录号WOS:000361903400024
项目编号81300756 ; 7132219
资助机构Chinese State Natural and Science Foundation ; Beijing Natural Science Foundation
引用统计
被引频次:5[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51964
专题北京大学第三临床医学院_眼科
北京大学第三临床医学院_骨科
作者单位1.Peking Univ, Hosp 3, Ctr Eye, Dept Ophthalmol, Beijing 100191, Peoples R China
2.Capital Med Univ, Beijing YouAn Hosp, Dept Ophthalmol, Beijing 100191, Peoples R China
3.4th Peoples Hosp Shenyang, Shenyang Inst Ophthalmol, Dept Ophthalmol, Shenyang 110031, Liaoning, Peoples R China
4.Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Ophthalmol, Shanghai 200127, Peoples R China
5.Univ Birmingham, Sch Psychol, Birmingham B15 2TT, W Midlands, England
6.Penn State Univ, Dept Neural & Behav Sci, Hershey, PA 17033 USA
7.Peking Univ, Hosp 3, Dept Ophthalmol, Beijing 100191, Peoples R China
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GB/T 7714
Wong, Mansin,Li, Ying,Li, Shang,et al. Therapeutic Retrobulbar Inhibition of STAT3 Protects Ischemic Retina Ganglion Cells[J]. MOLECULAR NEUROBIOLOGY,2015,52(3):1364-1377.
APA Wong, Mansin.,Li, Ying.,Li, Shang.,Zhang, Shaodan.,Li, Weiyi.,...&Huang, Ping.(2015).Therapeutic Retrobulbar Inhibition of STAT3 Protects Ischemic Retina Ganglion Cells.MOLECULAR NEUROBIOLOGY,52(3),1364-1377.
MLA Wong, Mansin,et al."Therapeutic Retrobulbar Inhibition of STAT3 Protects Ischemic Retina Ganglion Cells".MOLECULAR NEUROBIOLOGY 52.3(2015):1364-1377.
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