May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Transcriptional and Functional Alteration During Oxidative Stress-induced Retinal Pigmented Epithelium Cell Senescence
Author Affiliations & Notes
  • F. Mascarelli
    Inserm U 598, Center Biomed des Cordeliers, Paris, France
  • F. Debacq-Chainiaux
    Laboratory of Biochemistry and Cellular Biology, University of Namur, Namur, Belgium
  • O. Toussaint
    Laboratory of Biochemistry and Cellular Biology, University of Namur, Namur, Belgium
  • J. Tréton
    Inserm U 598, Center Biomed des Cordeliers, Paris, France
  • A.-L. Glotin
    Inserm U 598, Center Biomed des Cordeliers, Paris, France
  • Footnotes
    Commercial Relationships F. Mascarelli, None; F. Debacq-Chainiaux, None; O. Toussaint, None; J. Tréton, None; A. Glotin, None.
  • Footnotes
    Support None.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 5051. doi:
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      F. Mascarelli, F. Debacq-Chainiaux, O. Toussaint, J. Tréton, A.-L. Glotin; Transcriptional and Functional Alteration During Oxidative Stress-induced Retinal Pigmented Epithelium Cell Senescence. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5051.

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

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Abstract

Purpose:: To investigate the trancriptional and functional modification of retinal pigmented epithelial cells during oxidative stress-induced senescence.

Methods:: ARPE-19 were submitted to chronic t-BHP-mediated oxidative stress to induce premature senescence. Cell senescence was characterized by analyzing cell morphology, cell viability and proliferation, cell cycle progression and senescence associated beta-galactosidase activity.The dualChip human aging, a low-density DNA array, and real time polymerase chain reaction (PCR) were used to analyze and quantify the effects of senescence on gene expression. Western blot analysis and functional assays were performed to confirm modification at the protein and biological levels, respectively.

Results:: Chronic sublethal oxidative stresses mediate RPE cell senescence. A wild regulation of genes involved in cell cycle, cell proliferation and DNA synthesis was detected in senescent RPE cells. Alteration in the expression of genes involved in cell structure and extracellular matrix was correlated with a de-differentiated state and altered function of senescent RPE cells. Change in the expression of genes encoding for proteins involved in proteolytic process was also observed.

Conclusions:: Oxidative stress-induced RPE cell senescence presents some transcriptional and functional alteration observed during age-related macular degeneration. Our results show that oxidative stress participates to the senescent phenotype of RPE cells and suggest that genes involved in this process may be of interest for developing more selective methods for treating RPE cell aging and retinal degeneration.This study was supported by the European Grant EVI-GenoRet (LSHG-CT-2005-512036).

Keywords: aging • retinal degenerations: cell biology • gene/expression 
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