April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
FOXO Protein Expression is Down-Regulated With Aging in the Lens
Author Affiliations & Notes
  • W. Huang
    Ophthalmology, Duke Eye Center, Durham, North Carolina
  • J. Qiu
    Ophthalmology, Duke Eye Center, Durham, North Carolina
  • I. Navarro
    Ophthalmology, Duke Eye Center, Durham, North Carolina
  • P. Gonzalez
    Ophthalmology, Duke Eye Center, Durham, North Carolina
  • P. Challa
    Ophthalmology, Duke Eye Center, Durham, North Carolina
  • Footnotes
    Commercial Relationships  W. Huang, None; J. Qiu, None; I. Navarro, None; P. Gonzalez, None; P. Challa, None.
  • Footnotes
    Support  NIH K23 EY014019, core grant EY01894, EY016228, EY05722, Research to Prevent Blindness (RPB) Sybil B. Harrington Scholar Award
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 4590. doi:
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    • Get Citation

      W. Huang, J. Qiu, I. Navarro, P. Gonzalez, P. Challa; FOXO Protein Expression is Down-Regulated With Aging in the Lens. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4590.

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

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Abstract
 
Purpose:
 

Cataracts are a leading cause of age-related blindness worldwide. With aging, accumulation of oxidized lens components and decreased efficiency of repair mechanisms can contribute to the development of lens opacities i.e. cataracts. FoxO (Forkhead box O) transcription factors play key roles in cellular resistance to oxidative stress. In response to oxidative stress, FoxO activity is regulated primarily through regulation of its protein levels, subcelluar localization and post-translational modifications. We hypothesized that FoxO expression in the lens is altered with aging. The purpose of this study was to study the change of FoxO activation in the aging lens.

 
Methods:
 

Lenses proteins were collected from DBA/2J mice at 3, and 18 months old. The 18 month old mice had advanced nuclear cataract formation. Immunoblot analysis of FoxO1, FoxO3a as well as the phosphorylated forms was performed. Alpha-tubulin was used as a loading control and all values were quantified using densitometry. Statistical analysis was performed using a 2-way analysis of variance and significance was assessed at the 0.05 level.

 
Results:
 

FoxO1, FoxO3a levels were decreased significantly (p<0.05) at 54% and 67% respectively in the aging lens. Also, a significant decrease of both phosphorylated forms of FoxO1 and FoxO3a at 41% and 78% respectively were observed in the aging lens.

 
Conclusions:
 

FoxO1, FoxO3a as well as their phosphorylated forms are down regulated with age in the rodent lens. FoxO proteins play essential roles in the cellular response to physiologic oxidative stress, enhanced survival of cells, and maintenance of long-term regenerative potential. Therefore, this implies that age-related down regulation of FoxO expression may contribute to cataract formation.  

 
Keywords: cataract • aging • phosphorylation 
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