Journal
GEROSCIENCE
Volume 43, Issue 6, Pages 2809-2833Publisher
SPRINGER
DOI: 10.1007/s11357-021-00457-4
Keywords
Aging; Age-related macular degeneration; Cellular senescence; Retina; Senolytic
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Eliminating senescent cells may be a potential novel therapeutic approach for all types of AMD, as clearing senescent retinal pigment epithelium cells can ameliorate retinal degeneration, providing new insights into the treatment of AMD.
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.
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