Document Detail


Dietary antioxidants prevent age-related retinal pigment epithelium actin damage and blindness in mice lacking αvβ5 integrin.
MedLine Citation:
PMID:  22178979     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the aging human eye, oxidative damage and accumulation of pro-oxidant lysosomal lipofuscin cause functional decline of the retinal pigment epithelium (RPE), which contributes to age-related macular degeneration. In mice with an RPE-specific phagocytosis defect due to lack of αvβ5 integrin receptors, RPE accumulation of lipofuscin suggests that the age-related blindness we previously described in this model may also result from oxidative stress. Cellular and molecular targets of oxidative stress in the eye remain poorly understood. Here we identify actin among 4-hydroxynonenal (HNE) adducts formed specifically in β5(-/-) RPE but not in neural retina with age. HNE modification directly correlated with loss of resistance of actin to detergent extraction, suggesting cytoskeletal damage in aging RPE. Dietary enrichment with natural antioxidants, grapes or marigold extract containing macular pigments lutein/zeaxanthin, was sufficient to prevent HNE-adduct formation, actin solubility, lipofuscin accumulation, and age-related cone and rod photoreceptor dysfunction in β5(-/-) mice. Acute generation of HNE adducts directly destabilized actin but not tubulin cytoskeletal elements of RPE cells. These findings identify destabilization of the actin cytoskeleton as a consequence of a physiological, sublethal oxidative burden of RPE cells in vivo that is associated with age-related blindness and that can be prevented by consuming an antioxidant-rich diet.
Authors:
Chia-Chia Yu; Emeline F Nandrot; Ying Dun; Silvia C Finnemann
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-12-08
Journal Detail:
Title:  Free radical biology & medicine     Volume:  52     ISSN:  1873-4596     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-27     Completed Date:  2012-05-17     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  660-70     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Actin Cytoskeleton / metabolism*
Aldehydes / metabolism
Animals
Antioxidants / therapeutic use*
Apoptosis
Blindness / pathology,  prevention & control*
Cells, Cultured
Dietary Supplements
Electroretinography
Lipofuscin / metabolism
Macular Degeneration / pathology,  prevention & control
Male
Mice
Mice, 129 Strain
Mice, Knockout
Oxidation-Reduction
Photoreceptor Cells, Vertebrate / physiology
Phytotherapy*
Plant Preparations / therapeutic use*
Protein Carbonylation / drug effects
Protein Stability
Receptors, Vitronectin / deficiency*,  genetics
Retina / pathology
Retinal Pigment Epithelium / drug effects,  metabolism,  pathology
Vitis
Grant Support
ID/Acronym/Agency:
EY013295/EY/NEI NIH HHS; R01 EY013295/EY/NEI NIH HHS; R01 EY013295-11/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Aldehydes; 0/Antioxidants; 0/Lipofuscin; 0/Plant Preparations; 0/Receptors, Vitronectin; 0/integrin alphaVbeta5; 29343-52-0/4-hydroxy-2-nonenal
Comments/Corrections

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