|Dietary antioxidants prevent age-related retinal pigment epithelium actin damage and blindness in mice lacking αvβ5 integrin.|
|PMID: 22178979 Owner: NLM Status: MEDLINE|
|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.|
|Chia-Chia Yu; Emeline F Nandrot; Ying Dun; Silvia C Finnemann|
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|Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-12-08|
|Title: Free radical biology & medicine Volume: 52 ISSN: 1873-4596 ISO Abbreviation: Free Radic. Biol. Med. Publication Date: 2012 Feb|
|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|
|Languages: eng Pagination: 660-70 Citation Subset: IM|
|Copyright © 2011 Elsevier Inc. All rights reserved.|
|APA/MLA Format Download EndNote Download BibTex|
Aldehydes / metabolism
Antioxidants / therapeutic use*
Blindness / pathology, prevention & control*
Lipofuscin / metabolism
Macular Degeneration / pathology, prevention & control
Mice, 129 Strain
Photoreceptor Cells, Vertebrate / physiology
Plant Preparations / therapeutic use*
Protein Carbonylation / drug effects
Receptors, Vitronectin / deficiency*, genetics
Retina / pathology
Retinal Pigment Epithelium / drug effects, metabolism, pathology
|EY013295/EY/NEI NIH HHS; R01 EY013295/EY/NEI NIH HHS; R01 EY013295-11/EY/NEI NIH HHS|
|0/Aldehydes; 0/Antioxidants; 0/Lipofuscin; 0/Plant Preparations; 0/Receptors, Vitronectin; 0/integrin alphaVbeta5; 29343-52-0/4-hydroxy-2-nonenal|
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