Amyloid-β(1-42) alters structure and function of retinal pigmented epithelial cells
| العنوان: | Amyloid-β(1-42) alters structure and function of retinal pigmented epithelial cells |
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| المؤلفون: | Julien Bruban, Laurent Jonet, Frédéric Mascarelli, Na An, Anne-Lise Glotin, Naima Chalour, Virginie Dinet, Anne Marie Faussat, Florian Sennlaub |
| المصدر: | Aging Cell. 8:162-177 |
| بيانات النشر: | Wiley, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | cis-trans-Isomerases, Retinal degeneration, Aging, Retinal Pigment Epithelium, Drusen, Biology, Occludin, Cell Line, Tight Junctions, Macular Degeneration, Mice, chemistry.chemical_compound, medicine, Animals, Humans, Eye Proteins, Cytoskeleton, Membrane Potential, Mitochondrial, Retina, Amyloid beta-Peptides, Retinal, Hypertrophy, Cell Biology, medicine.disease, Actin cytoskeleton, Peptide Fragments, eye diseases, Cell biology, Mice, Inbred C57BL, Oxidative Stress, medicine.anatomical_structure, RPE65, chemistry, sense organs, Carrier Proteins, Reactive Oxygen Species, Photoreceptor Cells, Vertebrate |
| الوصف: | Age-related macular degeneration (AMD) is characterized by the formation of drusen, extracellular deposits associated with atrophy of the retinal pigmented epithelium (RPE), disturbance of the transepithelial barrier and photoreceptor death. Amyloid-beta (Abeta) is present in drusen but its role during AMD remains unknown. This study investigated the in vitro and in vivo effects of the oligomeric form of Abeta(1-42) - OAbeta(1-42) - on RPE and found that it reduced mitochondrial redox potential and increased the production of reactive oxygen species, but did not induce apoptosis in RPE cell cultures. It also disorganized the actin cytoskeleton and halved occludin expression, markedly decreasing attachment capacity and abolishing the selectivity of RPE cell transepithelial permeability. Antioxidant pretreatment partially reversed the effects of OAbeta(1-42) on mitochondrial redox potential and transepithelial permeability. Subretinally injected OAbeta(1-42) induced pigmentation loss and RPE hypertrophy but not RPE cell apoptosis in C57BL/6 J mice. Rapid OAbeta(1-42)-induced disorganization of cytoskeletal actin filaments was accompanied by decreased RPE expression of the tight junction proteins occludin and zonula occludens-1 and of the visual cycle proteins cellular retinaldehyde-binding protein and RPE65. The number of photoreceptors decreased by half within a few days. Our study pinpoints the role of Abeta in RPE alterations and dysfunctions leading to retinal degeneration and suggests that targeting Abeta may help develop selective methods for treating diseases involving retinal degeneration, such as AMD. |
| تدمد: | 1474-9726 1474-9718 |
| DOI: | 10.1111/j.1474-9726.2009.00456.x |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f8139b9d87e8768d9c445c0795528789 https://doi.org/10.1111/j.1474-9726.2009.00456.x |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f8139b9d87e8768d9c445c0795528789 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14749726 14749718 |
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| DOI: | 10.1111/j.1474-9726.2009.00456.x |