title: Myelination transition zone astrocytes are constitutively phagocytic and have synuclein dependent reactivity in glaucoma.
abstract: Optic nerve head (ONH) astrocytes have been proposed to play both protective and deleterious roles in glaucoma. We now show that, within the postlaminar ONH myelination transition zone (MTZ), there are astrocytes that normally express Mac-2 (also known as Lgals3 or galectin-3), a gene typically expressed only in phagocytic cells. Surprisingly, even in healthy mice, MTZ and other ONH astrocytes constitutive internalize large axonal evulsions that contain whole organelles. In mouse glaucoma models, MTZ astrocytes further up-regulate Mac-2 expression. During glaucomatous degeneration, there are dystrophic processes in the retina and optic nerve, including the MTZ, which contain protease resistant γ-synuclein. The increased Mac-2 expression by MTZ astrocytes during glaucoma likely depends on this γ-synuclein, as mice lacking γ-synuclein fail to up-regulate Mac-2 at the MTZ after elevation of intraocular pressure. These results suggest the possibility that a newly discovered normal degradative pathway for axons might contribute to glaucomatous neurodegeneration.
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Judy V
authors.initials: JV
authors.lastname: Nguyen
authors.forename: Ileana
authors.initials: I
authors.lastname: Soto
authors.forename: Keun-Young
authors.initials: KY
authors.lastname: Kim
authors.forename: Eric A
authors.initials: EA
authors.lastname: Bushong
authors.forename: Ericka
authors.initials: E
authors.lastname: Oglesby
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Valiente-Soriano
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yang
authors.forename: Chung-ha O
authors.initials: CH
authors.lastname: Davis
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Bedont
authors.forename: Janice L
authors.initials: JL
authors.lastname: Son
authors.forename: John O
authors.initials: JO
authors.lastname: Wei
authors.forename: Vladimir L
authors.initials: VL
authors.lastname: Buchman
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Zack
authors.forename: Manuel
authors.initials: M
authors.lastname: Vidal-Sanz
authors.forename: Mark H
authors.initials: MH
authors.lastname: Ellisman
authors.forename: Nicholas
authors.initials: N
authors.lastname: Marsh-Armstrong
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D001369:Axons / Q000378:metabolism / Q000473:pathology; D037502:Galectin 3 / Q000378:metabolism*; D005901:Glaucoma / Q000378:metabolism / Q000503:physiopathology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009413:Nerve Fibers, Myelinated / Q000378:metabolism*; D009900:Optic Nerve / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology*; D051845:gamma-Synuclein / Q000378:metabolism*
chemical_list: D037502:Galectin 3; C485095:Lgals3 protein, mouse; D051845:gamma-Synuclein