June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Molecular events for Bax activation in retinal cell death induced by all-trans-retinal
Author Affiliations & Notes
  • Osamu Sawada
    Ophthalmology, Case Western Reseve University, Cleveland, OH
    Ophthalmology, Shiga University of Medical Science, Otsu, Japan
  • Akiko Maeda
    Ophthalmology, Case Western Reseve University, Cleveland, OH
    Pharmacology, Case western Reserve University, Cleveland, OH
  • Shigemi Matsuyama
    Pharmacology, Case western Reserve University, Cleveland, OH
    Medicine; Division of Hematology and Oncology, Case Western Reserve University, Cleveland, OH
  • Tadao Maeda
    Ophthalmology, Case Western Reseve University, Cleveland, OH
    Pharmacology, Case western Reserve University, Cleveland, OH
  • Footnotes
    Commercial Relationships Osamu Sawada, None; Akiko Maeda, None; Shigemi Matsuyama, None; Tadao Maeda, QLT Inc (C)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1779. doi:
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    • Get Citation

      Osamu Sawada, Akiko Maeda, Shigemi Matsuyama, Tadao Maeda; Molecular events for Bax activation in retinal cell death induced by all-trans-retinal. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1779.

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

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Abstract

Purpose: Excess accumulation of all-trans-retinal (atRAL) after intense light exposure has been observed to cause apoptotic retinal cell death. Both oxidative stress and activation of the Bcl-2-associated X protein (Bax) have been implicated in atRAL induced cell death. However, a suitable relationship between these events remains unclear. The aim of this study is to seek molecular targets that are sensitive to oxidative stress in the retina, and subsequently cause retinal cell death via Bax activation.

Methods: Bax activation, phosphorylation of p53 at Ser46 which regulates the ability of p53 to induce apoptosis, and DNA damage by oxidative stress were evaluated after incubation with atRAL in ARPE19 cells using immunocytochemistry in vitro. Furthermore, these events were examined in retinas of Abca4-/-Rdh8-/- mice after intense light exposure or with aging using immunohistochemistry in vivo. Bax activation, phosphorylated-p53 at Ser46, and 8-hydroxy-2’-deoxyguanosine (8-OHdG), an indicator of oxidative DNA damage were monitored by anti-activated Bax antibody (6A7), anti-phosphorylated-p53 (Ser46) antibody, and anti-8-OHdG antibody, respectively.

Results: Increased signal intensity indicates Bax activation, increased phosphorylatation of p53 at Ser46, and DNA damage after atRAL incubation in ARPE19 cells. Bax activation, phosphorylation of p53 at Ser46, and DNA damage were additionally found in retinas of Abca4-/-Rdh8-/- mice after light exposure and those of Abca4-/-Rdh8-/- mice at 6 months of age.

Conclusions: DNA damage caused by oxidative stress and the subsequent phosphorylation of p53 can trigger Bax activation in retinal cell death process induced by atRAL.

Keywords: 426 apoptosis/cell death • 695 retinal degenerations: cell biology • 688 retina  
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