April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Optic Nerve Head Astrocytes Constitutively Phagocytose Material Extruded From Axons
Author Affiliations & Notes
  • Nicholas Marsh-Armstrong
    Neuroscience and Ophthalmology, Johns Hopkins Univ Sch of Med, Baltimore, Maryland
    Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, Maryland
  • Eric A. Bushong
    National Center for Microscopy and Imaging Research, Center for Research in Biological Systems, San Diego, California
  • Keun-Young Kim
    National Center for Microscopy and Imaging Research, Center for Research in Biological Systems, San Diego, California
  • Chung-ha O. Davis
    Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, Maryland
  • Mark H. Ellisman
    National Center for Microscopy and Imaging Research, Center for Research in Biological Systems, San Diego, California
    Neuroscience, University of California San Diego, San Diego, California
  • Footnotes
    Commercial Relationships  Nicholas Marsh-Armstrong, None; Eric A. Bushong, None; Keun-Young Kim, None; Chung-ha O. Davis, None; Mark H. Ellisman, None
  • Footnotes
    Support  Catalyst for a Cure grant from the Glaucoma Research Foundation (NM), NCRR grant 5P41RR004050 (MHE), and the International Retina Research Foundation and Lasker Foundation (MHE and NM)
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 5322. doi:https://doi.org/
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      Nicholas Marsh-Armstrong, Eric A. Bushong, Keun-Young Kim, Chung-ha O. Davis, Mark H. Ellisman; Optic Nerve Head Astrocytes Constitutively Phagocytose Material Extruded From Axons. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5322. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : We have previously shown that optic nerve head myelination transition zone (MTZ) astrocytes express a marker associated with phagocytosis. This study aimed to determine whether any optic nerve head astrocytes show structural evidence of phagocytosis, both in normal mice and mice undergoing glaucomatous degeneration.

Methods: : Scanning block-face serial electron microscopy (EM) was used to analyze blocks of optic nerve heads approximately 1.5 million µm3 in size from 9 m C57BL/6J, DBA/2J and DBA/2J Gpnmb+ mice. A novel labeling procedure for optimal resolution in scanning block-face serial EM was developed based on osmium thiocarboydrazide, lead aspartate and uranyl acetate en bloc labeling. Large volumes were reconstructed and analyzed using IMOD and UCSD-developed software tools.

Results: : Even in non-glaucomatous C57BL/6J nerves, axons at the glial lamina and MTZ had accumulations of electron dense granules bulging out from axons (protrusions) or fully separated from the axons and surrounded by astrocytes (evulsions). Similar bodies were also found within astrocytes at various stages of degradation. Accumulations at the MTZ were fewer in number (72 versus 218 in equal volumes) and generally of comparable size (0.9 +/- 0.2 µm at the lamina and 1.0 +/- 0.4 µm at the MTZ). However, evulsions at the MTZ differed from those at the lamina in that some contained myelin debris, and some were very large in size. Protrusions and evulsions were also more common and more variable in nerves amid glaucomatous degeneration.

Conclusions: : Optic nerve head astrocytes at the lamina region and MTZ manifest constitutive internalization of membrane-bounded organellar material from axons, even in non-glaucomatous mice such as C57BL/6J. The presence of an apparently constitutative transcytosis mechanism at the optic nerve head is highly surprising. This hereto unknown physiological process may play a prominent role in development of sectorial axonal degeneration which is characteristic of glaucoma.

Keywords: astrocytes: optic nerve head 
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