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