March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Myelination Transition Zone Astrocytes Manifest Lipid-processing Related Changes In Glaucoma
Author Affiliations & Notes
  • Nicholas Marsh-Armstrong
    Neuroscience and Ophthalmology, Johns Hopkins Univ Sch of Med, Baltimore, Maryland
  • Judy V. Nguyen
    Neuroscience and Ophthalmology, Johns Hopkins Univ Sch of Med, Baltimore, Maryland
  • Chung-ha O. Davis
    Neuroscience and Ophthalmology, Johns Hopkins Univ Sch of Med, Baltimore, Maryland
  • Pooja Karukonda
    Neuroscience and Ophthalmology, Johns Hopkins Univ Sch of Med, Baltimore, Maryland
  • Eric Bushong
    Neuroscience, University of San Diego, National Center for Microscopy and Imaging Research, San Diego, California
  • Keun-Young Kim
    Neuroscience, University of San Diego, National Center for Microscopy and Imaging Research, San Diego, California
  • Mark Ellisman
    Neuroscience, University of San Diego, National Center for Microscopy and Imaging Research, San Diego, California
  • Footnotes
    Commercial Relationships  Nicholas Marsh-Armstrong, None; Judy V. Nguyen, None; Chung-ha O. Davis, None; Pooja Karukonda, None; Eric Bushong, None; Keun-Young Kim, None; Mark Ellisman, None
  • Footnotes
    Support  Glaucoma Research Foundation and EY019960-01A1
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 3876. doi:
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      Nicholas Marsh-Armstrong, Judy V. Nguyen, Chung-ha O. Davis, Pooja Karukonda, Eric Bushong, Keun-Young Kim, Mark Ellisman; Myelination Transition Zone Astrocytes Manifest Lipid-processing Related Changes In Glaucoma. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3876.

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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 (ONH) astrocytes, including those at the myelination transition zone (MTZ), phagocytose axonal material even in normal healthy mice. In glaucoma animal models, the MTZ astrocytes increase expression of Mac-2, a marker associated with phagocytosis. In order to determine whether axonal phagocytosis by astrocytes is altered in glaucoma, we have analyzed molecular and structural evidence at the MTZ in the DBA/2J mouse glaucoma model.

Methods: : Longitudinal sections of ONHs from Gpnmb+ DBA/2J (control) mice and DBA/2J mice were analyzed with molecular markers associated with lipid processing (Adipose Differentiation Related Protein (Adrp) and Apolipoprotein-D (ApoD) mRNA) and an antibody that recognizes MBP in degenerating myelin, as well as the previously reported Mac-2 protein, using imaging multiple-segmentation based quantification methods. The ONH of Gpnmb+ DBA/2J mice and DBA/2J mice with mild or severe axonal degeneration were also analyzed by block-face scanning electron microscopy (BFSEM).

Results: : In 9-10 month-old (m) animals, the labeling for degenerating MBP and ApoD, as well as Mac-2, peaked at the MTZ in the non-diseased Gpnmb+ DBA/2J mice and all three were upregulated in DBA/2J mice (p<0.005, p<0.006 and p<0.009, respectively). Surprisingly, both normal and upregulated ApoD mRNA was found nearly exclusively within oligodendrocytes. Adrp expression was shown to normally peak at the MTZ, but then to be upregulated (p<0.05) in a pattern that did not match the upregulation patterns of Mac-2 or the microglia marker Iba-1. BFSEM showed that MTZ normally internalize segments of myelin, and that in DBA/2J mice contain lipid droplets early and heterogenous debris late in the degeneration.

Conclusions: : The oligodendrocytes at the MTZ of normal mice express markers that both distinguish them from other oligodendrocytes and which are increased in animal models of glaucoma. This supports the view that the MTZ constantly experiences milder forms of the insult or insults that blind in glaucoma. MTZ astrocytes internalize and degrade myelin, and have lipid droplet accumulations early in the disease. This suggests that the normal phagocytosis of myelin by astrocytes at the MTZ may become dysfunctional early in glaucoma.

Keywords: astrocyte • optic nerve 
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