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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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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.
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.
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.
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.
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