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

Nguyen, J. V., Soto, I., Kim, K.-Y., Bushong, E. A., Oglesby, E., Valiente-Soriano, F. J., Yang, Z., Davis, C.-H. O., Bedont, J. L., Son, J. L., Wei, J. O., Buchman, Vladimir L., Zack, D. J., Vidal-Sanz, M., Ellisman, M. H. and Marsh-Armstrong, N. 2011. Myelination transition zone astrocytes are constitutively phagocytic and have synuclein dependent reactivity in glaucoma. Proceedings of the National Academy of Sciences 108 (3) , pp. 1176-1181. 10.1073/pnas.1013965108

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > Q Science (General)
Uncontrolled Keywords: DBA/2J mice; retinal ganglion cell; Sncg
Publisher: The National Academy of Sciences of the USA
ISSN: 0027-8424
Last Modified: 04 Jun 2017 03:31
URI: http://orca.cf.ac.uk/id/eprint/22394

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