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

Yang Hu, Kevin Park, Liu Yang, Xin Wei, Qiang Yang, Kin Sang Cho, Peter Thielen, Ann Hwee Lee, Romain Cartoni, LaurieH Glimcher, DongFeng Chen, Zhigang He

Research output: Contribution to journalArticle

102 Citations (Scopus)

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

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Unfolded Protein Response
Retinal Ganglion Cells
Axons
CCAAT-Enhancer-Binding Proteins
Wounds and Injuries
Optic Nerve Injuries
Nerve Crush
Axotomy
Vincristine
Optic Nerve
Intraocular Pressure
Cell Survival
Cell Death
Up-Regulation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Differential effects of unfolded protein response pathways on axon injury-induced death of retinal ganglion cells. / Hu, Yang; Park, Kevin; Yang, Liu; Wei, Xin; Yang, Qiang; Cho, Kin Sang; Thielen, Peter; Lee, Ann Hwee; Cartoni, Romain; Glimcher, LaurieH; Chen, DongFeng; He, Zhigang.

In: Neuron, Vol. 73, No. 3, 09.02.2012, p. 445-452.

Research output: Contribution to journalArticle

Hu, Y, Park, K, Yang, L, Wei, X, Yang, Q, Cho, KS, Thielen, P, Lee, AH, Cartoni, R, Glimcher, L, Chen, D & He, Z 2012, 'Differential effects of unfolded protein response pathways on axon injury-induced death of retinal ganglion cells', Neuron, vol. 73, no. 3, pp. 445-452. https://doi.org/10.1016/j.neuron.2011.11.026
Hu, Yang ; Park, Kevin ; Yang, Liu ; Wei, Xin ; Yang, Qiang ; Cho, Kin Sang ; Thielen, Peter ; Lee, Ann Hwee ; Cartoni, Romain ; Glimcher, LaurieH ; Chen, DongFeng ; He, Zhigang. / Differential effects of unfolded protein response pathways on axon injury-induced death of retinal ganglion cells. In: Neuron. 2012 ; Vol. 73, No. 3. pp. 445-452.
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