Therapeutic Retrobulbar Inhibition of STAT3 Protects Ischemic Retina Ganglion Cells

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• 作者：Mansin Wong ; Ying Li ; Shang Li ; Shaodan Zhang ; Weiyi Li…
• 关键词：Optic nerve head ; Astrocyte ; Astrogliosis ; JAK/STAT3 pathway ; Neuroprotection ; Glaucoma
• 刊名：Molecular Neurobiology
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：52
• 期：3
• 页码：1364-1377
• 全文大小：9,001 KB
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• 作者单位：Mansin Wong (1)
  Ying Li (1)
  Shang Li (2)
  Shaodan Zhang (1) (3)
  Weiyi Li (1) (4)
  Pei Zhang (1)
  Chaoran Chen (5)
  Colin J. Barnstable (6)
  Samuel S. Zhang (6)
  Chun Zhang (1)
  Ping Huang (1) (7)
  
  1. Department of Ophthalmology, Peking University Eye Center, Peking University Third Hospital, Beijing, 100191, China
  2. Department of Ophthalmology, Beijing YouAn Hospital, Capital Medical University, Beijing, 100191, China
  3. Department of Ophthalmology, Shenyang Institute of Ophthalmology, The 4th People鈥檚 Hospital of Shenyang, Liaoning, 110031, China
  4. Department of Ophthalmology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China
  5. School of Psychology, University of Birmingham, Birmingham, B15 2TT, UK
  6. Department of Neural & Behavioral Sciences, Pennsylvania State University, Hershey, PA, 17033, USA
  7. Department of Ophthalmology, Peking University Third Hospital, 49 North Huayuan Road, Beijing, 100191, China
  
• 刊物主题：Neurosciences; Neurobiology; Cell Biology; Neurology;
• 出版者：Springer US
• ISSN：1559-1182

文摘

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. Keywords Optic nerve head Astrocyte Astrogliosis JAK/STAT3 pathway Neuroprotection Glaucoma