title: Subtype-specific regeneration of retinal ganglion cells following axotomy: effects of osteopontin and mTOR signaling.
abstract: In mammals, few retinal ganglion cells (RGCs) survive following axotomy, and even fewer regenerate axons. This could reflect differential extrinsic influences or the existence of subpopulations that vary in their responses to injury. We tested these alternatives by comparing responses of molecularly distinct subsets of mouse RGCs to axotomy. Survival rates varied dramatically among subtypes, with alpha-RGCs (αRGCs) surviving preferentially. Among survivors, αRGCs accounted for nearly all regeneration following downregulation of PTEN, which activates the mTOR pathway. αRGCs have uniquely high mTOR signaling levels among RGCs and also selectively express osteopontin (OPN) and receptors for the insulin-like growth factor 1 (IGF-1). Administration of OPN plus IGF-1 promotes regeneration as effectively as downregulation of PTEN; however, regeneration is still confined to αRGCs. Our results reveal dramatic subtype-specific differences in the ability of RGCs to survive and regenerate following injury, and they identify promising agents for promoting axonal regeneration.
authors.affiliation: Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Duan
authors.affiliation: Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
authors.forename: Mu
authors.initials: M
authors.lastname: Qiao
authors.affiliation: F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Bei
authors.affiliation: Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
authors.forename: In-Jung
authors.initials: IJ
authors.lastname: Kim
authors.affiliation: F.M. Kirby Neurobiology Center, Department of Neurology, Boston 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
authors.affiliation: Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA. Electronic address: sanesj@mcb.harvard.edu.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Sanes
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D019771:Axotomy / Q000379:methods; D002470:Cell Survival / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051379:Mice; D009416:Nerve Regeneration / Q000502:physiology*; D009900:Optic Nerve / Q000502:physiology; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C519530:insulin-like growth factor-1, mouse; D053495:Osteopontin; D007334:Insulin-Like Growth Factor I; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases