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

Research output: Contribution to journalArticlepeer-review

368 Scopus citations


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 languageEnglish
Pages (from-to)617-623
Number of pages7
Issue number5
StatePublished - Dec 10 2009
Externally publishedYes




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