title: Spermidine promotes retinal ganglion cell survival and optic nerve regeneration in adult mice following optic nerve injury.
abstract: Spermidine acts as an endogenous free radical scavenger and inhibits the action of reactive oxygen species. In this study, we examined the effects of spermidine on retinal ganglion cell (RGC) death in a mouse model of optic nerve injury (ONI). Daily ingestion of spermidine reduced RGC death following ONI and sequential in vivo retinal imaging revealed that spermidine effectively prevented retinal degeneration. Apoptosis signal-regulating kinase-1 (ASK1) is an evolutionarily conserved mitogen-activated protein kinase kinase kinase and has an important role in ONI-induced RGC apoptosis. We demonstrated that spermidine suppresses ONI-induced activation of the ASK1-p38 mitogen-activated protein kinase pathway. Moreover, production of chemokines important for microglia recruitment was decreased with spermidine treatment and, consequently, accumulation of retinal microglia is reduced. In addition, the ONI-induced expression of inducible nitric oxide synthase in the retina was inhibited with spermidine treatment, particularly in microglia. Furthermore, daily spermidine intake enhanced optic nerve regeneration in vivo. Our findings indicate that spermidine stimulates neuroprotection as well as neuroregeneration, and may be useful for treatment of various neurodegenerative diseases including glaucoma.
authors.affiliation: 1] Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan [2] Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Noro
authors.affiliation: Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Namekata
authors.affiliation: Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kimura
authors.affiliation: Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: X
authors.initials: X
authors.lastname: Guo
authors.affiliation: Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Azuchi
authors.affiliation: Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Harada
authors.affiliation: Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakano
authors.affiliation: Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tsuneoka
authors.affiliation: Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: T
authors.identifier: 0000000161670997
authors.initials: T
authors.lastname: Harada
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration / Q000187:drug effects*; D020221:Optic Nerve Injuries / Q000188:drug therapy* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D013095:Spermidine / Q000494:pharmacology*
chemical_list: D013095:Spermidine