TY - JOUR
T1 - SOCS3 Deletion Promotes Optic Nerve Regeneration In Vivo
AU - Smith, Patrice D.
AU - Sun, Fang
AU - Park, Kevin Kyungsuk
AU - Cai, Bin
AU - Wang, Chen
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
Y1 - 2009/12/10
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.
AB - 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.
KW - MOLNEURO
KW - SIGNALING
UR - http://www.scopus.com/inward/record.url?scp=71149106854&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2009.11.021
DO - 10.1016/j.neuron.2009.11.021
M3 - Article
C2 - 20005819
AN - SCOPUS:71149106854
SN - 0896-6273
VL - 64
SP - 617
EP - 623
JO - Neuron
JF - Neuron
IS - 5
ER -