April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
DBA/2J Mitochondria Morphology and Distribution Varies With Age and Increasing IOP
Author Affiliations & Notes
  • D. M. Inman
    Neurological Surgery, University of Washington, Seattle, Washington
  • J. M. Knox
    Neurological Surgery, University of Washington, Seattle, Washington
  • R. S. Morrison
    Neurological Surgery, University of Washington, Seattle, Washington
  • P. J. Horner
    Neurological Surgery, University of Washington, Seattle, Washington
  • Footnotes
    Commercial Relationships  D.M. Inman, None; J.M. Knox, None; R.S. Morrison, None; P.J. Horner, None.
  • Footnotes
    Support  The Glaucoma Research Foundation and The Melza M. and Frank Theodore Barr Foundation to P.J.H; and the National Institutes of Health NS35533 and NS056031 to R.S.M.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2140. doi:
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      D. M. Inman, J. M. Knox, R. S. Morrison, P. J. Horner; DBA/2J Mitochondria Morphology and Distribution Varies With Age and Increasing IOP. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2140.

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

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Purpose: : Retinal ganglion cell axons degenerate in glaucoma. In the DBA/2J mouse model of glaucoma, the slowest conducting, smallest caliber axons degenerate concomitant with significant decreases in optic nerve ATP levels. In general, there is a positive relationship between mitochondrial size and potential energy output: larger mitochondria make more ATP. Additionally, position and number of mitochondria can provide insight into metabolic health and energetic capacity. We undertook an analysis of mitochondria in the DBA/2J optic nerve in order to determine whether the age and IOP-dependent ATP deficit is intrinsic to the RGC axon.

Methods: : Longitudinal electron micrographs of mitochondria in DBA/2J optic nerve at 3, 6, 10 months were compared to age-matched C57Bl/6 optic nerve micrographs. Mitochondria in digitized EM negatives were analyzed using ImageJ.

Results: : Mitochondria numbers peak at 6 months of age in the DBA/2J optic nerve, and remain constant through 10 months of age. This contrasts with C57Bl/6 RGC axons, in which a significant decrease in mitochondrial number from 6 to 10 months was observed. Mitochondria size (length and width) varied in RGC axons of DBA/2J but not C57Bl/6. The distance between mitochondria is similar across all ages in the DBA/2J, while the distance between mitochondria at 6 months is significantly greater in DBA/2J than in the C57Bl/6 RGC axons. In DBA/2J axons at 6 months, solitary mitochondria within an axon are more prevalent; however, when multiple mitochondria are observed, they are in close proximity. There are more mitochondria clusters at 10 months in C57Bl/6, though the distance between adjacent mitochondria has increased with age. The proximity of mitochondria to the axon membrane in the DBA/2J RGC axons decreases with age while it increases in C57Bl/6. DBA/2J mitochondria are on the whole further from the axon membrane than C57Bl/6 mitochondria.

Conclusions: : Decreases in mitochondria size in DBA/2J RGC axons with age suggest decreased energetic potential. Fewer clusters of mitochondria in DBA/2 RGC axons suggest reduced potential for fusion and/or incidence of fission events within the mitochondrial population. This lower dynamism could significantly impact RGC axon response to stress.

Keywords: mitochondria • optic nerve • aging 

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