Document Detail

Prematurely senescent ARPE-19 cells display features of age-related macular degeneration.
MedLine Citation:
PMID:  18226607     Owner:  NLM     Status:  MEDLINE    
The etiology of age-related macular degeneration (AMD), the leading cause of blindness in the developed world, remains poorly understood, but may be related to cumulative oxidative stress. The prime target of the disease is the retinal pigmented epithelium (RPE). To study the molecular mechanisms underlying RPE degeneration, we investigated whether repetitive oxidative stress induced premature senescence in RPE cells from the human ARPE-19 cell line. After exposure to 8 mM tert-butylhydroperoxide (tert-BHP) for 1 h daily for 5 days, the cells showed four well-known senescence biomarkers: hypertrophy, senescence-associated beta-galactosidase activity, growth arrest, and cell cycle arrest in G1. A specific low-density array followed by qRT-PCR validation allowed us to identify 36 senescence-associated genes differentially expressed in the prematurely senescent cells. Functional analysis demonstrated that premature senescence induced amyloid beta secretion, resistance to acute stress by tert-BHP and amyloid beta, and defects in adhesion and transepithelial permeability. Coculture assays with choroidal endothelial cells showed the proangiogenic properties of the senescent RPE cells. These results demonstrate that chronic oxidative stress induces premature senescence in RPE cells that modifies the transcriptome and substantially alters cell processes involved in the pathophysiology of AMD. Oxidative stress-induced premature senescence may represent an in vitro model for screening therapeutics against AMD and other retinal degeneration disorders.
Anne-Lise Glotin; Florence Debacq-Chainiaux; Jean-Yves Brossas; Anne-Marie Faussat; Jacques Tréton; Anna Zubielewicz; Olivier Toussaint; Frédéric Mascarelli
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-01-28
Journal Detail:
Title:  Free radical biology & medicine     Volume:  44     ISSN:  0891-5849     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-31     Completed Date:  2008-06-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1348-61     Citation Subset:  IM    
Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, UMR S 872, Paris F-75006, France.
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MeSH Terms
Cell Aging*
Cell Line
Free Radicals
Macular Degeneration / metabolism*,  pathology*
Models, Biological
Neovascularization, Pathologic
Oxidative Stress
Oxygen / metabolism
Retina / pathology
Tight Junctions
Transcription, Genetic
tert-Butylhydroperoxide / pharmacology
Reg. No./Substance:
0/Free Radicals; 75-91-2/tert-Butylhydroperoxide; 7782-44-7/Oxygen

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