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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. doi: https://doi.org/.
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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
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
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
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
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