Zeng Bing, Zhang Chuanhe, Liang Yifan, Huang Jianguo, Li Deshuang, Liu Ziling, Liao Hongxia, Yang Tedu, Liu Muyun, Zou Chang, Liu Dongcheng, Qin Bo
Shenzhen Aier Eye Hospital, Aier Eye Hospital, Jinan University, Shenzhen, China.
Shenzhen Aier Ophthalmic Technology Institute, Shenzhen, China.
iScience. 2025 Apr 17;28(5):112464. doi: 10.1016/j.isci.2025.112464. eCollection 2025 May 16.
The main challenge in dissecting the cells and pathways involved in the pathogenesis of age-related macular degeneration (AMD) is the highly heterogeneous and dynamic nature of the retinal microenvironment. This study aimed to describe the comprehensive landscape of the dry AMD (dAMD) model and identify the key cell cluster contributing to dAMD. We identified a subset of Müller cells that express high levels of Sox2, which play crucial roles in homeostasis and neuroprotection in both mouse models of AMD and patients with dAMD. Additionally, the number of Sox2 Müller cells decreased significantly during the progression of AMD, indicating these cells were damaged and underwent cell death. Interestingly, ferroptosis and apoptosis were identified as contributors to the damage of Sox2 Müller cells. Our findings are potentially valuable not only for advancing the current understanding of dAMD progression but also for the development of treatment strategies through the protection of Müller cells.
剖析与年龄相关性黄斑变性（AMD）发病机制相关的细胞和信号通路的主要挑战在于视网膜微环境具有高度的异质性和动态性。本研究旨在描绘干性AMD（dAMD）模型的全貌，并确定导致dAMD的关键细胞簇。我们鉴定出了一组表达高水平Sox2的 Müller 细胞，它们在 AMD 小鼠模型和 dAMD 患者的体内平衡和神经保护中发挥着关键作用。此外，在AMD进展过程中，Sox2 Müller细胞的数量显著减少，表明这些细胞受到损伤并发生了细胞死亡。有趣的是，铁死亡和细胞凋亡被确定为导致Sox2 Müller细胞损伤的因素。我们的研究结果不仅对推动目前对dAMD进展的理解具有潜在价值，而且对于通过保护Müller细胞来制定治疗策略也具有潜在价值。
