Differential effects of unfolded protein response pathways on axon injury-induced death of retinal ganglion cells

Yang Hu, Kevin K. Park, Liu Yang, Xin Wei, Qiang Yang, Kin Sang Cho, Peter Thielen, Ann Hwee Lee, Romain Cartoni, Laurie H. Glimcher, Dong Feng Chen, Zhigang He

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108 Scopus citations

Abstract

Loss of retinal ganglion cells (RGCs) accounts for visual function deficits after optic nerve injury, but how axonal insults lead to neuronal death remains elusive. By using an optic nerve crush model that results in the death of the majority of RGCs, we demonstrate that axotomy induces differential activation of distinct pathways of the unfolded protein response in axotomized RGCs. Optic nerve injury provokes a sustained CCAAT/enhancer binding homologous protein (CHOP) upregulation, and deletion of CHOP promotes RGC survival. In contrast, IRE/XBP-1 is only transiently activated, and forced XBP-1 activation dramatically protects RGCs from axon injury-induced death. Importantly, such differential activations of CHOP and XBP-1 and their distinct effects on neuronal cell death are also observed in RGCs with other types of axonal insults, such as vincristine treatment and intraocular pressure elevation, suggesting a new protective strategy for neurodegeneration associated with axonal damage.

Original languageEnglish (US)
Pages (from-to)445-452
Number of pages8
JournalNeuron
Volume73
Issue number3
DOIs
StatePublished - Feb 9 2012

ASJC Scopus subject areas

  • Neuroscience(all)

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    Hu, Y., Park, K. K., Yang, L., Wei, X., Yang, Q., Cho, K. S., Thielen, P., Lee, A. H., Cartoni, R., Glimcher, L. H., Chen, D. F., & He, Z. (2012). Differential effects of unfolded protein response pathways on axon injury-induced death of retinal ganglion cells. Neuron, 73(3), 445-452. https://doi.org/10.1016/j.neuron.2011.11.026