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.
authors.affiliation: F.M. Kirby Neurobiology Center, Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Smith
authors.forename: Fang
authors.initials: F
authors.lastname: Sun
authors.forename: Kevin Kyungsuk
authors.initials: KK
authors.lastname: Park
authors.forename: Bin
authors.initials: B
authors.lastname: Cai
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Kuwako
authors.forename: Irene
authors.initials: I
authors.lastname: Martinez-Carrasco
authors.forename: Lauren
authors.initials: L
authors.lastname: Connolly
authors.forename: Zhigang
authors.initials: Z
authors.lastname: He
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism; D002772:Cholera Toxin / Q000378:metabolism; D020934:Ciliary Neurotrophic Factor / Q000235:genetics / Q000494:pharmacology; D050822:Cytokine Receptor gp130 / Q000172:deficiency; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D007276:Injections, Intraventricular / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009416:Nerve Regeneration / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D020221:Optic Nerve Injuries / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D009924:Organ Culture Techniques; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000473:pathology / Q000502:physiology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000172:deficiency* / Q000502:physiology; D058570:TOR Serine-Threonine Kinases; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D020934:Ciliary Neurotrophic Factor; C494200:Il6st protein, mouse; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014404:Tubulin; C462941:beta3 tubulin, mouse; D050822:Cytokine Receptor gp130; D049452:Green Fluorescent Proteins; D002772:Cholera Toxin; D017853:Phosphotransferases (Alcohol Group Acceptor); C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases