April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Neuroprotection by AG490 in a rat transient retina ischemia/reperfusion model: disruption of STAT3 phosphorylation in astrocyte cells of the optic nerve
Author Affiliations & Notes
  • Ping Huang
    Peking University Third Hospital, Beijing, China
  • ManSin Wong
    Peking University Third Hospital, Beijing, China
  • Ting Deng
    Peking University Third Hospital, Beijing, China
  • Shaodan Zhang
    Peking University Third Hospital, Beijing, China
  • Samuel Shaomin Zhang
    Neural & Behavioral Sciences, Penn State University, Hershey, PA
  • Chun Zhang
    Peking University Third Hospital, Beijing, China
  • Footnotes
    Commercial Relationships Ping Huang, None; ManSin Wong, None; Ting Deng, None; Shaodan Zhang, None; Samuel Shaomin Zhang, None; Chun Zhang, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 2433. doi:
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      Ping Huang, ManSin Wong, Ting Deng, Shaodan Zhang, Samuel Shaomin Zhang, Chun Zhang; Neuroprotection by AG490 in a rat transient retina ischemia/reperfusion model: disruption of STAT3 phosphorylation in astrocyte cells of the optic nerve. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2433.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

To determine the role of STAT3 signaling in the reactivation of optic nerve astrocytes in vivo, and to investigate the potential influence on optic nerve and retinal ganglion cell (RGC) damage

 
Methods
 

Three groups of Wistar rats (200-250g) were used: Normal group (without surgery, n=12), I/R group (n=48), and I/R+AG490 group (n=48). In I/R and I/R+AG490 groups, transient ischemia/reperfusion (I/R) model was established in the right eye, retrobulbar injection were given either with AG490 (10mM) or dilution vehicle DMSO 5 times respectively before surgery, 1st, 2nd, 4th and 7th day after surgery. Samples of optic nerve and retina were collected at 2nd, 3rd, 7th and 14th day post-surgery. Western blot analysis and immunohistochemistry were used to observe the effect of JAK/STAT3 inhibition, astrocyte reactivation, and optic nerve and RGC damage

 
Results
 

Retrobulbar application of AG490 leads to (i) decreased astrocyte reactivation in the optic nerve from day 2 post-injury, (ii) decreased remodeling of astrocytes in the optic nerve throughout the tested time window, (iii) increased nerve fiber bundle survival in the optic nerve, (iv) increased nerve fiber bundle and RGC survival in the retina, and (v) no influence of astrocyte reactivation in the retina

 
Conclusions
 

JAK/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

     
Keywords: 431 astroglia: optic nerve head • 615 neuroprotection  
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