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Myelination transition zone astrocytes are constitutively phagocytic and have synuclein dependent reactivity in glaucoma.

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.

Pubmed ID: 21199938

Authors

  • Nguyen JV
  • Soto I
  • Kim KY
  • Bushong EA
  • Oglesby E
  • Valiente-Soriano FJ
  • Yang Z
  • Davis CH
  • Bedont JL
  • Son JL
  • Wei JO
  • Buchman VL
  • Zack DJ
  • Vidal-Sanz M
  • Ellisman MH
  • Marsh-Armstrong N

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

January 18, 2011

Associated Grants

  • Agency: Wellcome Trust, Id: 075615
  • Agency: Wellcome Trust, Id: 075615/Z/04/z
  • Agency: NCRR NIH HHS, Id: 5P41RR004050
  • Agency: NEI NIH HHS, Id: 5R01EY019305
  • Agency: NIGMS NIH HHS, Id: 5R01GM82949
  • Agency: NEI NIH HHS, Id: 5R21EY019737
  • Agency: NEI NIH HHS, Id: 5T32 EY07143-12
  • Agency: NIDA NIH HHS, Id: DA016602
  • Agency: NEI NIH HHS, Id: T32 EY017203

Mesh Terms

  • Animals
  • Astrocytes
  • Axons
  • Galectin 3
  • Glaucoma
  • Immunohistochemistry
  • In Situ Hybridization
  • Mice
  • Microscopy, Electron, Scanning
  • Nerve Fibers, Myelinated
  • Optic Nerve
  • Phagocytosis
  • gamma-Synuclein