April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Mice With A mtDNA-linked Respiratory Chain Defect Show Increased Neuronal Injury Consequent To IOP Stress
Author Affiliations & Notes
  • Nicole J. Van Bergen
    Glaucoma Research Unit, Centre for Eye Research Australia, East Melbourne, Australia
  • George Kong
    Glaucoma Research Unit, Centre for Eye Research Australia, East Melbourne, Australia
  • Vicki Chrysostomou
    Glaucoma Research Unit, Centre for Eye Research Australia, East Melbourne, Australia
  • Ian Trounce
    Glaucoma Research Unit, Centre for Eye Research Australia, East Melbourne, Australia
  • Jonathon Crowston
    Glaucoma Research Unit, Centre for Eye Research Australia, East Melbourne, Australia
  • Footnotes
    Commercial Relationships  Nicole J. Van Bergen, None; George Kong, None; Vicki Chrysostomou, None; Ian Trounce, None; Jonathon Crowston, None
  • Footnotes
    Support  Glaucoma Australia; Henry Greenfield Research Fund; Edols Trust Fund.
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2439. doi:
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    • Get Citation

      Nicole J. Van Bergen, George Kong, Vicki Chrysostomou, Ian Trounce, Jonathon Crowston; Mice With A mtDNA-linked Respiratory Chain Defect Show Increased Neuronal Injury Consequent To IOP Stress. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2439.

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

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Abstract

Purpose: : Our previous work has demonstrated that retinal ganglion cells of old mice (12 and 18-month) have increased vulnerability to short term IOP elevation compared to young (3-month) mice. To determine whether age-associated mitochondrial dysfunction might contribute to this increased vulnerability, we here investigated whether a novel mouse with impairment in mitochondrial OXPHOS also has increased the susceptibility to IOP elevation.

Methods: : Mice harbouring interspecific mtDNA mutations (Xeno-mito mice) on a C57BL6 background and strain-matched controls were subjected to full-field (ganzfeld) scotopic electroretinogram (ERG) to assess retinal function at baseline and during IOP elevation (50mm Hg for 30 minutes, n>8 mice). To characterize the mitochondrial defect in the retina and brain of these mice, we measured retinal and brain mitochondrial respiration (n=6) with the Oroboros Oxygraph 2k. We also quantified OXPHOS protein levels by western blotting.

Results: : Xeno-mito (n>6) mice showed a 52% greater loss of ganglion cell function, in response to IOP stress, and a delayed recovery compared to age-matched wild type mice. (p<0.05) which persisted at one week and was associated with increased oxidative stress, demonstrated by elevated HO-1. Detailed investigation of OXPHOS in the retina and brain demonstrated a significant decrease in complex I driven ATP production with mitochondrial respiration decreased by 18% in 12 month Xenos (p=0.019) and by 16% in 18+ month Xenos (p=0.020). There was also a 55% decreased complex I expression (p<0.05) in the retina. Other complexes were not significantly altered, with the exception of complex IV which appeared upregulated in the xeno-mito mice.

Conclusions: : Defective OXPHOS complex-1 impairs retinal function in these mice and increases vulnerability to IOP elevation. The Xeno-mito mice provide insight into the in vivo effects mtDNA-linked OXPHOS defects on neural retinal function and may provide further mechanistic insight into how age-related mitochondrial failure may contribute to ganglion cell vulnerability to IOP elevation.

Keywords: mitochondria • retina • optic nerve 
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