衰老会导致小鼠视网膜色素上皮细胞的丧失和吞噬体处理能力的下降。
Aging induces cell loss and a decline in phagosome processing in the mouse retinal pigment epithelium.
机构信息
Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Australia.
Department of Anatomy and Physiology, The University of Melbourne, Melbourne, Australia.
出版信息
Neurobiol Aging. 2023 Aug;128:1-16. doi: 10.1016/j.neurobiolaging.2023.03.003. Epub 2023 Mar 13.
Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss and dysfunction in the retinal pigment epithelium (RPE) with age is known to contribute to disease development. The aim of this study was to investigate how the C57BL/6J mouse RPE changes with age. RPE structure was found to change with age and eccentricity, with cell size increasing, nuclei lost, and tight junctions altered in the peripheral retina. Phagocytosis of photoreceptor outer segments (POS) by the RPE was investigated using gene expression analysis and histology. RNA-Seq transcriptomic gene profiling of the RPE showed a downregulation of genes involved in phagosome processing and histological analysis showed a decline in phagosome-lysosome association in the aged tissue. In addition, failures in the autophagy pathway that modulates intracellular waste degradation were observed in the aged RPE tissue. These findings highlight that RPE cell loss and slowing of POS processing contribute to RPE dysfunction with age and may predispose the aging eye to AMD development.
年龄相关性黄斑变性（AMD）是一种导致视网膜色素上皮（RPE）不可逆转的视力丧失和功能障碍的主要原因，众所周知，随着年龄的增长，RPE 的退化会导致疾病的发展。本研究旨在探讨 C57BL/6J 小鼠 RPE 随年龄的变化。研究发现，RPE 的结构随年龄和偏心度的变化而变化，在外周视网膜中，细胞大小增加，细胞核丢失，紧密连接改变。通过基因表达分析和组织学研究，研究了 RPE 对光感受器外节（POS）的吞噬作用。RPE 的 RNA-Seq 转录组基因谱分析显示，参与吞噬体加工的基因下调，组织学分析显示，老化组织中吞噬体-溶酶体的关联减少。此外，还观察到衰老的 RPE 组织中自噬途径的故障，该途径调节细胞内废物的降解。这些发现强调了 RPE 细胞的丧失和 POS 处理的减缓导致了年龄相关性 RPE 功能障碍，并可能使衰老的眼睛容易发生 AMD 的发展。
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