Targeting senescent retinal pigment epithelial cells facilitates retinal regeneration in mouse models of age-related macular degeneration

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Title
Targeting senescent retinal pigment epithelial cells facilitates retinal regeneration in mouse models of age-related macular degeneration
Author(s)
J B Chae; H Jang; C Son; C W Park; H Choi; S Jin; Ho-Yeon Lee; H Lee; J H Ryu; Namshin Kim; C Kim; H Chung
Bibliographic Citation
Geroscience, vol. 43, no. 6, pp. 2809-2833
Publication Year
2021
Abstract
Although age-related macular degeneration (AMD) is a multifactorial disorder with angiogenic, immune, and inflammatory components, the most common clinical treatment strategies are antiangiogenic therapies. However, these strategies are only applicable to neovascular AMD, which accounts for less than 20% of all AMD cases, and there are no FDA-approved drugs for the treatment of dry AMD, which accounts for ~ 80% of AMD cases. Here, we report that the elimination of senescent cells is a potential novel therapeutic approach for the treatment of all types of AMD. We identified senescent retinal pigment epithelium (RPE) cells in animal models of AMD and determined their contributions to retinal degeneration. We further confirmed that the clearance of senescent RPE cells with the MDM2-p53 inhibitor Nutlin-3a ameliorated retinal degeneration. These findings provide new insights into the use of senescent cells as a therapeutic target for the treatment of AMD.
Keyword
AgingAge-related macular degenerationCellular senescenceRetinaSenolytic
ISSN
2509-2715
Publisher
Springer
DOI
http://dx.doi.org/10.1007/s11357-021-00457-4
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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