SOCS3 Deletion Promotes Optic Nerve Regeneration In Vivo
Copyright policy )SOCS3 Deletion Promotes Optic Nerve Regeneration In Vivo
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.
- Harvard Medical School United States
- Carleton University Canada
- Harvard University United States
Analysis of Variance, Cholera Toxin, Dose-Response Relationship, Drug, Neuroscience(all), Green Fluorescent Proteins, Mice, Transgenic, MOLNEURO, Axons, Nerve Regeneration, Mice, Inbred C57BL, Disease Models, Animal, Mice, Phosphotransferases (Alcohol Group Acceptor), Organ Culture Techniques, Animals, Newborn, Gene Expression Regulation, SIGNALING, Optic Nerve Injuries, Cytokine Receptor gp130, Animals, Ciliary Neurotrophic Factor, Carrier Proteins, Injections, Intraventricular
Analysis of Variance, Cholera Toxin, Dose-Response Relationship, Drug, Neuroscience(all), Green Fluorescent Proteins, Mice, Transgenic, MOLNEURO, Axons, Nerve Regeneration, Mice, Inbred C57BL, Disease Models, Animal, Mice, Phosphotransferases (Alcohol Group Acceptor), Organ Culture Techniques, Animals, Newborn, Gene Expression Regulation, SIGNALING, Optic Nerve Injuries, Cytokine Receptor gp130, Animals, Ciliary Neurotrophic Factor, Carrier Proteins, Injections, Intraventricular
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