title: Restoration of Visual Function by Enhancing Conduction in Regenerated Axons.
abstract: Although a number of repair strategies have been shown to promote axon outgrowth following neuronal injury in the mammalian CNS, it remains unclear whether regenerated axons establish functional synapses and support behavior. Here, in both juvenile and adult mice, we show that either PTEN and SOCS3 co-deletion, or co-overexpression of osteopontin (OPN)/insulin-like growth factor 1 (IGF1)/ciliary neurotrophic factor (CNTF), induces regrowth of retinal axons and formation of functional synapses in the superior colliculus (SC) but not significant recovery of visual function. Further analyses suggest that regenerated axons fail to conduct action potentials from the eye to the SC due to lack of myelination. Consistent with this idea, administration of voltage-gated potassium channel blockers restores conduction and results in increased visual acuity. Thus, enhancing both regeneration and conduction effectively improves function after retinal axon injury.
authors.affiliation: F.M. Kirby Neurobiology Center, Department of Neurology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Bei
authors.affiliation: F.M. Kirby Neurobiology Center, Department of Neurology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Henry Hing Cheong
authors.initials: HHC
authors.lastname: Lee
authors.affiliation: F.M. Kirby Neurobiology Center, Department of Neurology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Liu
authors.affiliation: F.M. Kirby Neurobiology Center, Department of Neurology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Georgia
authors.initials: G
authors.lastname: Gunner
authors.affiliation: F.M. Kirby Neurobiology Center, Department of Neurology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Neurosurgery, ChangZheng Hospital, 415 FengYang Road, Shanghai 200003, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Jin
authors.affiliation: F.M. Kirby Neurobiology Center, Department of Neurology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Long
authors.initials: L
authors.lastname: Ma
authors.affiliation: F.M. Kirby Neurobiology Center, Department of Neurology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, ChangZheng Hospital, 415 FengYang Road, Shanghai 200003, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Hou
authors.affiliation: F.M. Kirby Neurobiology Center, Department of Neurology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
authors.forename: Takao K
authors.initials: TK
authors.lastname: Hensch
authors.affiliation: Department of Physiology, Tufts University, Boston, MA 02111, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Frank
authors.affiliation: Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Sanes
authors.affiliation: F.M. Kirby Neurobiology Center, Department of Neurology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Chinfei
authors.initials: C
authors.lastname: Chen
authors.affiliation: F.M. Kirby Neurobiology Center, Department of Neurology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA. Electronic address: michela.fagiolini@childrens.harvard.edu.
authors.forename: Michela
authors.initials: M
authors.lastname: Fagiolini
authors.affiliation: F.M. Kirby Neurobiology Center, Department of Neurology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA. Electronic address: zhigang.he@childrens.harvard.edu.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: He
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism; D055724:Electrophysiological Phenomena; D005123:Eye / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism; D009900:Optic Nerve; D053495:Osteopontin / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects; D013477:Superior Colliculi / Q000502:physiology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D013569:Synapses
chemical_list: D020934:Ciliary Neurotrophic Factor; D026902:Potassium Channel Blockers; C491411:Socs3 protein, mouse; C506896:Spp1 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C519530:insulin-like growth factor-1, mouse; D053495:Osteopontin; D007334:Insulin-Like Growth Factor I; D015761:4-Aminopyridine; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse