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Abstract #59420 Published in IGR 16-3

Therapeutic Retrobulbar Inhibition of STAT3 Protects Ischemic Retina Ganglion Cells

Wong M; Li Y; Li S; Zhang S; Li W; Zhang P; Chen C; Barnstable CJ; Zhang SS; Zhang C; Huang P
Molecular Neurobiology 2015; 52: 1364-1377

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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.

Department of Ophthalmology, Peking University Eye Center, Peking University Third Hospital, Beijing, 100191, China.

Full article

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Classification:

5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
11.8 Neuroprotection (Part of: 11 Medical treatment)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
3.6 Cellular biology (Part of: 3 Laboratory methods)

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