May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Endogenous ROS Production Increases and Mitochondrial Redox Function Decreases in the RPE as a Function of Age and Stage of AMD
Author Affiliations & Notes
  • H. Xu
    Ophthalmology, UTMB, Galveston, Texas
  • X. Zhong
    Ophthalmology, UTMB, Galveston, Texas
  • H. Lin
    Ophthalmology, UTMB, Galveston, Texas
  • B. F. Godley
    Ophthalmology, UTMB, Galveston, Texas
  • M. E. Boulton
    Ophthalmology, UTMB, Galveston, Texas
  • Footnotes
    Commercial Relationships  H. Xu, None; X. Zhong, None; H. Lin, None; B.F. Godley, None; M.E. Boulton, None.
  • Footnotes
    Support  NIH EY12850
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 230. doi:https://doi.org/
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      H. Xu, X. Zhong, H. Lin, B. F. Godley, M. E. Boulton; Endogenous ROS Production Increases and Mitochondrial Redox Function Decreases in the RPE as a Function of Age and Stage of AMD. Invest. Ophthalmol. Vis. Sci. 2008;49(13):230. doi: https://doi.org/.

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

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Abstract

Purpose: : To determine whether the endogenous production of reactive oxygen species (ROS) is associated with a decrease in mitochondrial redox function in RPE aging and the pathogenesis of AMD.

Methods: : Macular and peripheral RPE cells were isolated and cultured from human donor eyes of different ages and from AMD patients graded according to the Minnesota Grading System. The production of ROS in RPE cells was detected by MitoSOXTM Red mitochondrial superoxide indicator (Molecular Probes). Redox function and complex IV activity of confluent RPE cultures was assessed using MTT assay and Rapid Microplate Assay for complex IV activity respectively. To test the vulnerability of RPE cells to oxidative stress, RPE cells were exposed to hydrogen peroxide (H2O2, 200 µM) for 1 hour.

Results: : Endogenous ROS generation in the RPE increased as a function of donor age and stage of AMD. This correlated with a decrease in mitochondria redox function and complex IV activity. Redox function of macular RPE cells from young (20-30yr) donors was 35% greater than that of RPE cells from old donors (70-90 yr). Mitochondria redox function and Complex IV activity in macular RPE were significantly lower compared to peripheral RPE cells (p<0.01). Mitochondria redox function decreased in RPE cells with the progression of AMD compared to age-matched normal donors and this decrease was greatest in advanced AMD (p<0.05). Treatment with a sublethal dose of H2O2 (200 µM) for 1 hr resulted in a greater decrease in mitochondrial redox function for old donors compared to that of young donors (p<0.05) and this decline in mitochondrial redox function in cells exposed to oxidative stress was even greater in macular RPE cells from AMD donors with the greatest decrease at the advanced stages of AMD.

Conclusions: : The increased generation of endogeneous ROS with increasing age may be responsible for the decline of mitochondria function and this may contribute to RPE dysfunction in AMD. This suggests that RPE aging and dysfunction may be prevented by mitochondrial-targeted antioxidants.

Keywords: age-related macular degeneration • mitochondria • retinal pigment epithelium 
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