Department of Ophthalmology, Konkuk University School of Medicine, Seoul, South Korea.
Department of Chemistry, Ulsan National Institute of Science and Technology, Ulsan, South Korea.
Geroscience. 2021 Dec;43(6):2809-2833. doi: 10.1007/s11357-021-00457-4. Epub 2021 Oct 2.
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.
虽然年龄相关性黄斑变性（AMD）是一种多因素疾病，具有血管生成、免疫和炎症成分，但最常见的临床治疗策略是抗血管生成疗法。然而，这些策略仅适用于新生血管性 AMD，占所有 AMD 病例的不到 20%，而对于占 AMD 病例约 80%的干性 AMD，尚无 FDA 批准的治疗药物。在这里，我们报告称，消除衰老细胞是治疗所有类型 AMD 的一种潜在新的治疗方法。我们在 AMD 的动物模型中鉴定出衰老的视网膜色素上皮（RPE）细胞，并确定了它们对视网膜变性的贡献。我们进一步证实，用 MDM2-p53 抑制剂 Nutlin-3a 清除衰老的 RPE 细胞可改善视网膜变性。这些发现为将衰老细胞作为治疗 AMD 的治疗靶点提供了新的见解。
