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Amyloid-beta(1-42) alters structure and function of retinal pigmented epithelial cells.
- Source :
-
Aging cell [Aging Cell] 2009 Apr; Vol. 8 (2), pp. 162-77. Date of Electronic Publication: 2009 Feb 23. - Publication Year :
- 2009
-
Abstract
- 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.
- Subjects :
- Aging metabolism
Aging pathology
Amyloid beta-Peptides metabolism
Animals
Carrier Proteins drug effects
Carrier Proteins metabolism
Cell Line
Cytoskeleton drug effects
Cytoskeleton metabolism
Cytoskeleton pathology
Eye Proteins drug effects
Eye Proteins metabolism
Humans
Hypertrophy chemically induced
Hypertrophy metabolism
Hypertrophy physiopathology
Macular Degeneration chemically induced
Macular Degeneration metabolism
Membrane Potential, Mitochondrial drug effects
Membrane Potential, Mitochondrial physiology
Mice
Mice, Inbred C57BL
Oxidative Stress physiology
Peptide Fragments metabolism
Photoreceptor Cells, Vertebrate drug effects
Photoreceptor Cells, Vertebrate metabolism
Photoreceptor Cells, Vertebrate pathology
Reactive Oxygen Species metabolism
Retinal Pigment Epithelium metabolism
Tight Junctions drug effects
Tight Junctions metabolism
Tight Junctions pathology
cis-trans-Isomerases
Amyloid beta-Peptides toxicity
Macular Degeneration physiopathology
Oxidative Stress drug effects
Peptide Fragments toxicity
Retinal Pigment Epithelium drug effects
Retinal Pigment Epithelium pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1474-9726
- Volume :
- 8
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Aging cell
- Publication Type :
- Academic Journal
- Accession number :
- 19239420
- Full Text :
- https://doi.org/10.1111/j.1474-9726.2009.00456.x