April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Neurochemistry of RGC Axonal Dystrophies in the DBA/2J Mouse Model of Glaucoma
Author Affiliations & Notes
  • S. E. MacNamee
    Ophthalmology, Vanderbilt University, Nashville, Tennessee
  • B. Petty
    Ophthalmology, Vanderbilt University, Nashville, Tennessee
  • S. D. Crish
    Ophthalmology, Vanderbilt University, Nashville, Tennessee
  • D. J. Calkins
    Ophthalmology, Vanderbilt University, Nashville, Tennessee
  • Footnotes
    Commercial Relationships  S.E. MacNamee, None; B. Petty, None; S.D. Crish, None; D.J. Calkins, None.
  • Footnotes
    Support  NIH Grant EY017427, AHAF Glaucoma Research Grant , and the Melza M. and Frank Theodore Barr Foundation through the Glaucoma Research Foundation Catalyst for a Cure
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 2767. doi:
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      S. E. MacNamee, B. Petty, S. D. Crish, D. J. Calkins; Neurochemistry of RGC Axonal Dystrophies in the DBA/2J Mouse Model of Glaucoma. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2767.

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

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Purpose: : Axonal dystrophies in neurodegenerations demonstrate a characteristic morphology and neurochemistry that varies depending on etiology. We examined retinal ganglion cell axons in the optic projection of the DBA/2J mouse model of glaucoma for protein indicators that have been implicated in the pathogenesis and injury response in other neurodegenerative disorders.

Methods: : Brains were harvested from aldehyde-perfused DBA/2J mice between 3 and 22 months of age, sectioned in the coronal plane, and immuno-stained for different phosphoisoforms of heavy-chain neurofilament (NF-H), the axonal marker tubulin, the anterograde transport motor kinesin, and axonal growth associated protein-43 (GAP-43).

Results: : While axonal dystrophies could be present at any age in the optic nerve and tract, their likelihood increased with increasing age. Axonal dystrophies occurred either as a series of swellings along continuous axons or as a large, single varicosity marking the end bulb of a degenerating axon. Dystrophies varied in size up to 10µm in diameter and contained accumulations of various cytoskeletal elements, including tubulin, phosphorylated NF-H (SMI-31), and hyperphosphorylated NF-H (SMI-34) as well as kinesin. Large varicosities in the optic tract that strongly stained for GAP-43 were found in animals as old as 22 months. GAP-43+ varicosities were absent in young (3-5 months) animals.

Conclusions: : As in other neurodegenerative disorders, axonal dystrophies in the DBA/2J mouse contain large accumulations of cytoskeletal proteins and kinesin indicative of compromised axonal transport. Hyperphosphorylation of NF-H (SMI-34) is thought to be a causative factor in the development of axonal transport deficits, known to be relevant in the DBA/2J. GAP-43 accumulations evident in the optic tract even at very advanced ages suggest that distal axonal plasticity may represent a potential therapeutic target in glaucoma.

Keywords: degenerations/dystrophies • optic nerve • regeneration 

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