title: Artemin augments survival and axon regeneration in axotomized retinal ganglion cells.
abstract: Artemin, a recently discovered member of the glial cell line-derived neurotrophic factor (GDNF) family, has neurotrophic effects on damaged neurons, including sympathetic neurons, dopamine neurons, and spiral ganglion neurons both in vivo and in vitro. However, its effects on retinal cells and its intracellular signaling remain relatively unexplored. During development, expression of GFRα3, a specific receptor for artemin, is strong in the immature retina and gradually decreases during maturation, suggesting a possible role in the formation of retinal connections. Optic nerve damage in mature rats causes levels of GFRα3 mRNA to increase tenfold in the retina within 3 days. GFRα3 mRNA levels continue to rise within the first week and then decline. Artemin, a specific ligand for GFRα3, has a neuroprotective effect on axotomized retinal ganglion cells (RGCs) in vivo and in vitro via activation of the extracellular signal-related kinase- and phosphoinositide 3-kinase-Akt signaling pathways. Artemin also has a substantial effect on axon regeneration in RGCs both in vivo and in vitro, whereas other GDNF family members do not. Therefore, artemin/GFRα3, but not other GDNF family members, may be of value for optic nerve regeneration in mature mammals.
authors.affiliation: Department of Ophthalmology and Visual Science, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Omodaka
authors.forename: Takuji
authors.initials: T
authors.lastname: Kurimoto
authors.forename: Orie
authors.initials: O
authors.lastname: Nakamura
authors.forename: Kota
authors.initials: K
authors.lastname: Sato
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yasuda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Noriko
authors.initials: N
authors.lastname: Himori
authors.forename: Yu
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Toru
authors.initials: T
authors.lastname: Nakazawa
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019771:Axotomy; D002478:Cells, Cultured; D002772:Cholera Toxin; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000627:therapeutic use*; D009901:Optic Nerve Diseases / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000473:pathology*; D013997:Time Factors; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: C490887:Artn protein, rat; D004791:Enzyme Inhibitors; C494989:Gfra1 protein, rat; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D014404:Tubulin; D002772:Cholera Toxin
keywords: glaucoma; growth factor; mitogen-activated protein kinase; optic nerve axotomy; regeneration; retinal ganglion cell; signal transduction