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

Judy V. Nguyen, Ileana Soto, Keun Young Kim, Eric A. Bushong, Ericka Oglesby, Francisco J. Valiente-Soriano, Zhiyong Yang, Chung Ha O. Davis, Joseph L. Bedont, Janice L. Son, John O. Wei, Vladimir L. Buchman, Donald J. Zack, Manuel Vidal-Sanz, Mark H. Ellisman, Nicholas Marsh-Armstrong

Research output: Contribution to journalArticlepeer-review

124 Scopus citations

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 upregulate 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 foraxonsmight contribute toglaucomatous neurodegeneration.

Original languageEnglish (US)
Pages (from-to)1176-1181
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number3
DOIs
StatePublished - Jan 18 2011
Externally publishedYes

Keywords

  • DBA/2J mice
  • Retinal ganglion cell
  • Sncg

ASJC Scopus subject areas

  • General

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