Therapeutic Retrobulbar Inhibition of STAT3 Protects Ischemic Retina Ganglion Cells

Mansin Wong, Ying Li, Shang Li, Shaodan Zhang, Weiyi Li, Pei Zhang, Chaoran Chen, Colin J. Barnstable, Samuel S. Zhang, Chun Zhang, Ping Huang

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1364-1377
Number of pages14
JournalMolecular Neurobiology
Volume52
Issue number3
DOIs
StatePublished - Dec 1 2015

Fingerprint

STAT3 Transcription Factor
Optic Nerve
Ganglia
Astrocytes
Retina
Retinal Ganglion Cells
Nerve Fibers
Therapeutics
Reperfusion
Ischemia
Janus Kinases
Nerve Degeneration
Optic Disk
Neurodegenerative Diseases
Glaucoma
Transcriptional Activation
Cell Survival
Pharmacology

All Science Journal Classification (ASJC) codes

  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Wong, M., Li, Y., Li, S., Zhang, S., Li, W., Zhang, P., ... Huang, P. (2015). Therapeutic Retrobulbar Inhibition of STAT3 Protects Ischemic Retina Ganglion Cells. Molecular Neurobiology, 52(3), 1364-1377. https://doi.org/10.1007/s12035-014-8945-9
Wong, Mansin ; Li, Ying ; Li, Shang ; Zhang, Shaodan ; Li, Weiyi ; Zhang, Pei ; Chen, Chaoran ; Barnstable, Colin J. ; Zhang, Samuel S. ; Zhang, Chun ; Huang, Ping. / Therapeutic Retrobulbar Inhibition of STAT3 Protects Ischemic Retina Ganglion Cells. In: Molecular Neurobiology. 2015 ; Vol. 52, No. 3. pp. 1364-1377.
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abstract = "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.",
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Wong, M, Li, Y, Li, S, Zhang, S, Li, W, Zhang, P, Chen, C, Barnstable, CJ, Zhang, SS, Zhang, C & Huang, P 2015, 'Therapeutic Retrobulbar Inhibition of STAT3 Protects Ischemic Retina Ganglion Cells', Molecular Neurobiology, vol. 52, no. 3, pp. 1364-1377. https://doi.org/10.1007/s12035-014-8945-9

Therapeutic Retrobulbar Inhibition of STAT3 Protects Ischemic Retina Ganglion Cells. / Wong, Mansin; Li, Ying; Li, Shang; Zhang, Shaodan; Li, Weiyi; Zhang, Pei; Chen, Chaoran; Barnstable, Colin J.; Zhang, Samuel S.; Zhang, Chun; Huang, Ping.

In: Molecular Neurobiology, Vol. 52, No. 3, 01.12.2015, p. 1364-1377.

Research output: Contribution to journalArticle

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