SOCS3 Deletion Promotes Optic Nerve Regeneration in Vivo

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2009 Dec 17

PMID 20005819

Citations 271

Authors

Patrice D Smith

Fang Sun

Kevin Kyungsuk Park

Bin Cai

Chen Wang

Kenichiro Kuwako

Irene Martinez-Carrasco

Lauren Connolly

Zhigang He

Affiliations

Soon will be listed here.

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.

Citing Articles

Predicting the Regenerative Potential of Retinal Ganglion Cells Based on Developmental Growth Trajectories.

Santos J, Li C, Andries L, Masin L, Nuttin B, Reinhard K bioRxiv. 2025; .

PMID: 40060504 PMC: 11888416. DOI: 10.1101/2025.02.28.640775.

Unlocking the potential for optic nerve regeneration over long distances: a multi-therapeutic intervention.

Liu Z, Zhou L, Sun Y, Ma Y, Liu C, Zhang B Front Neurol. 2025; 15():1526973.

PMID: 39850731 PMC: 11754882. DOI: 10.3389/fneur.2024.1526973.

Electric field stimulation directs target-specific axon regeneration and partial restoration of vision after optic nerve crush injury.

Kim T, Iseri E, Peng M, Medvidovic S, Silliman T, Pahlavan P PLoS One. 2025; 20(1):e0315562.

PMID: 39787061 PMC: 11717274. DOI: 10.1371/journal.pone.0315562.

Engineered bio-functional material-based nerve guide conduits for optic nerve regeneration: a view from the cellular perspective, challenges and the future outlook.

Obeng E, Shen B, Wang W, Xie Z, Zhang W, Li Z Regen Biomater. 2025; 12:rbae133.

PMID: 39776856 PMC: 11703557. DOI: 10.1093/rb/rbae133.

Marcks overexpression in retinal ganglion cells promotes optic nerve regeneration.

Peng X, Li Y, Gu C, He X, Li C, Sun Y Cell Death Dis. 2024; 15(12):906.

PMID: 39695101 PMC: 11655864. DOI: 10.1038/s41419-024-07281-6.

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