Dietary antioxidants prevent age-related retinal pigment epithelium actin damage and blindness in mice lacking αvβ5 integrin
| Autor: | Emeline F. Nandrot, Chia-Chia Yu, Silvia C. Finnemann, Ying Dun |
|---|---|
| Přispěvatelé: | Nandrot, Emeline, Fordham University, Department of Biological Sciences, Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
genetic structures Apoptosis Retinal Pigment Epithelium Protein oxidation medicine.disease_cause Blindness Biochemistry Antioxidants Protein Carbonylation chemistry.chemical_compound Macular Degeneration Mice 0302 clinical medicine Vitis Cytoskeleton Cells Cultured ComputingMilieux_MISCELLANEOUS Mice Knockout 0303 health sciences Protein Stability Cell biology Actin Cytoskeleton medicine.anatomical_structure [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs Oxidation-Reduction Photoreceptor Cells Vertebrate Mice 129 Strain Biology Retina Article 4-Hydroxynonenal Lipofuscin 03 medical and health sciences Physiology (medical) medicine Electroretinography Animals Receptors Vitronectin [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs 030304 developmental biology Aldehydes Retinal pigment epithelium Actin cytoskeleton eye diseases chemistry Dietary Supplements 030221 ophthalmology & optometry sense organs Plant Preparations Oxidative stress Phytotherapy |
| Zdroj: | Free Radical Biology and Medicine Free Radical Biology and Medicine, 2011, 52, pp.660-670. ⟨10.1016/j.freeradbiomed.2011.11.021⟩ Free Radical Biology and Medicine, Elsevier, 2011, 52, pp.660-670. ⟨10.1016/j.freeradbiomed.2011.11.021⟩ |
| ISSN: | 0891-5849 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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