SOCS3 Deletion Promotes Optic Nerve Regeneration In Vivo

Patrice D. Smith; Fang Sun; Kevin Kyungsuk Park; Bin Cai; Chen Wang; Kenichiro Kuwako; Irene Martinez-Carrasco; Lauren Connolly; Zhigang He

doi:10.1016/j.neuron.2009.11.021

SOCS3 Deletion Promotes Optic Nerve Regeneration In Vivo

Patrice D. Smith, Fang Sun, Kevin Kyungsuk Park, Bin Cai, Chen Wang, Kenichiro Kuwako, Irene Martinez-Carrasco, Lauren Connolly, Zhigang He^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

388 Scopus citations

Abstract

Axon regeneration failure accounts for permanent functional deficits following CNS injury in adult mammals. However, the underlying mechanisms remain elusive. In analyzing axon regeneration in different mutant mouse lines, we discovered that deletion of suppressor of cytokine signaling 3 (SOCS3) in adult retinal ganglion cells (RGCs) promotes robust regeneration of injured optic nerve axons. This regeneration-promoting effect is efficiently blocked in SOCS3-gp130 double-knockout mice, suggesting that SOCS3 deletion promotes axon regeneration via a gp130-dependent pathway. Consistently, a transient upregulation of ciliary neurotrophic factor (CNTF) was observed within the retina following optic nerve injury. Intravitreal application of CNTF further enhances axon regeneration from SOCS3-deleted RGCs. Together, our results suggest that compromised responsiveness to injury-induced growth factors in mature neurons contributes significantly to regeneration failure. Thus, developing strategies to modulate negative signaling regulators may be an efficient strategy of promoting axon regeneration after CNS injury.

Original language	English (US)
Pages (from-to)	617-623
Number of pages	7
Journal	Neuron
Volume	64
Issue number	5
DOIs	https://doi.org/10.1016/j.neuron.2009.11.021
State	Published - Dec 10 2009
Externally published	Yes

Funding

We thank Dr. K. Rajewsky for providing gp130 f/f mice and A. Yoshimura for providing SOCS3 f/f mice. This study was supported by grants from the Canadian Institutes of Health Research (to P.D.S.), Craig Nelson Foundation (to K.K.P.), NINDS, Wings for Life, and Adelson Medical Research Foundation (to Z.H.).

Keywords

MOLNEURO
SIGNALING

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuron.2009.11.021

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title = "SOCS3 Deletion Promotes Optic Nerve Regeneration In Vivo",

abstract = "Axon regeneration failure accounts for permanent functional deficits following CNS injury in adult mammals. However, the underlying mechanisms remain elusive. In analyzing axon regeneration in different mutant mouse lines, we discovered that deletion of suppressor of cytokine signaling 3 (SOCS3) in adult retinal ganglion cells (RGCs) promotes robust regeneration of injured optic nerve axons. This regeneration-promoting effect is efficiently blocked in SOCS3-gp130 double-knockout mice, suggesting that SOCS3 deletion promotes axon regeneration via a gp130-dependent pathway. Consistently, a transient upregulation of ciliary neurotrophic factor (CNTF) was observed within the retina following optic nerve injury. Intravitreal application of CNTF further enhances axon regeneration from SOCS3-deleted RGCs. Together, our results suggest that compromised responsiveness to injury-induced growth factors in mature neurons contributes significantly to regeneration failure. Thus, developing strategies to modulate negative signaling regulators may be an efficient strategy of promoting axon regeneration after CNS injury.",

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note = "Funding Information: We thank Dr. K. Rajewsky for providing gp130 f/f mice and A. Yoshimura for providing SOCS3 f/f mice. This study was supported by grants from the Canadian Institutes of Health Research (to P.D.S.), Craig Nelson Foundation (to K.K.P.), NINDS, Wings for Life, and Adelson Medical Research Foundation (to Z.H.). ",

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AU - Kuwako, Kenichiro

AU - Martinez-Carrasco, Irene

AU - Connolly, Lauren

AU - He, Zhigang

N1 - Funding Information: We thank Dr. K. Rajewsky for providing gp130 f/f mice and A. Yoshimura for providing SOCS3 f/f mice. This study was supported by grants from the Canadian Institutes of Health Research (to P.D.S.), Craig Nelson Foundation (to K.K.P.), NINDS, Wings for Life, and Adelson Medical Research Foundation (to Z.H.).

PY - 2009/12/10

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N2 - Axon regeneration failure accounts for permanent functional deficits following CNS injury in adult mammals. However, the underlying mechanisms remain elusive. In analyzing axon regeneration in different mutant mouse lines, we discovered that deletion of suppressor of cytokine signaling 3 (SOCS3) in adult retinal ganglion cells (RGCs) promotes robust regeneration of injured optic nerve axons. This regeneration-promoting effect is efficiently blocked in SOCS3-gp130 double-knockout mice, suggesting that SOCS3 deletion promotes axon regeneration via a gp130-dependent pathway. Consistently, a transient upregulation of ciliary neurotrophic factor (CNTF) was observed within the retina following optic nerve injury. Intravitreal application of CNTF further enhances axon regeneration from SOCS3-deleted RGCs. Together, our results suggest that compromised responsiveness to injury-induced growth factors in mature neurons contributes significantly to regeneration failure. Thus, developing strategies to modulate negative signaling regulators may be an efficient strategy of promoting axon regeneration after CNS injury.

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SOCS3 Deletion Promotes Optic Nerve Regeneration In Vivo

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Keywords

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