Intracellular amyloid-ß disrupts tight junctions of the retinal pigment epithelium via NF-κB activation.
Neurobiol Aging
; 95: 115-122, 2020 11.
Article
in En
| MEDLINE
| ID: mdl-32795848
ABSTRACT
Drusen are focal deposits between the retinal pigment epithelium (RPE) and Bruch's membrane in the retina of patients with age-related macular degeneration. Amyloid-ß is one of the important components of drusen, which leads to local inflammation. Furthermore, intracellular amyloid-ß disrupts tight junctions of the RPE. However, the intracellular mechanisms linking intracellular amyloid-ß and tight-junction disruption are not clear. In this study, intracellular amyloid-ß oligomers activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65, leading to the disorganization of tight junctions of the RPE in mice after subretinal injection of amyloid-ß. Amyloid-ß also triggered NF-κB activation in the RPE cells in confluent culture, which was inhibited by the suppression of the advanced glycosylation end product-specific receptor. NF-κB inhibition by an IκB kinase inhibitor prevented the suppression of expression of tight-junction proteins, zonula occuludens-1 and occludin in RPE cells. In addition, tight-junction complexes remained intact in the RPE of mice with NF-κB inhibition, although there were intracellular amyloid-ß oligomers. These data suggested that NF-κB inhibition might be a therapeutic approach to prevent amyloid-ß-mediated tight-junction disruption.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Amyloid beta-Peptides
/
NF-kappa B
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Tight Junctions
/
Retinal Pigment Epithelium
Limits:
Animals
Language:
En
Journal:
Neurobiol Aging
Year:
2020
Document type:
Article