Neurotoxic Reactive Astrocytes Drive Neuronal Death after Retinal Injury

神经毒性反应性星形胶质细胞在视网膜损伤后导致神经元死亡

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作者:Kevin A Guttenplan, Benjamin K Stafford, Rana N El-Danaf, Drew I Adler, Alexandra E Münch, Maya K Weigel, Andrew D Huberman, Shane A Liddelow

Abstract

Glaucoma is a neurodegenerative disease that features the death of retinal ganglion cells (RGCs) in the retina, often as a result of prolonged increases in intraocular pressure. We show that preventing the formation of neuroinflammatory reactive astrocytes prevents the death of RGCs normally seen in a mouse model of glaucoma. Furthermore, we show that these spared RGCs are electrophysiologically functional and thus still have potential value for the function and regeneration of the retina. Finally, we demonstrate that the death of RGCs depends on a combination of both an injury to the neurons and the presence of reactive astrocytes, suggesting a model that may explain why reactive astrocytes are toxic only in some circumstances. Altogether, these findings highlight reactive astrocytes as drivers of RGC death in a chronic neurodegenerative disease of the eye.

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