Translational Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada; Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Translational Biomedical Research Group, Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
Am J Pathol. 2024 Nov;194(11):2179-2193. doi: 10.1016/j.ajpath.2024.07.017. Epub 2024 Aug 13.
Biological processes throughout the body are orchestrated in time through the regulation of local circadian clocks. The retina is among the most metabolically active tissues, with demands depending greatly on the light/dark cycle. Most cell types within the rodent retina are known to express the circadian clock; however, retinal clock expression in humans has not previously been localized. Moreover, the effect of local circadian clock dysfunction on retinal homeostasis is incompletely understood. The current study indicated an age-dependent decline in circadian clock gene and protein expression in the human retina. An animal model of targeted Bmal1 deficiency was used to identify the circadian clock of the retinal Müller glia as essential for neuronal survival, vascular integrity, and retinal function. These results suggest a potential role for the local retinal circadian clock within the Müller glia in age-related retinal disease and retinal degeneration.
全身的生物过程通过局部生物钟的调节在时间上协调。视网膜是新陈代谢最活跃的组织之一，其需求在很大程度上取决于光/暗周期。已知啮齿动物视网膜中的大多数细胞类型都表达生物钟；然而，人类视网膜中的生物钟表达以前尚未定位。此外，局部生物钟功能障碍对视网膜内稳态的影响还不完全清楚。本研究表明，人类视网膜中的生物钟基因和蛋白表达随年龄增长而下降。使用靶向 Bmal1 缺陷的动物模型来确定视网膜 Müller 胶质细胞中的生物钟对于神经元存活、血管完整性和视网膜功能至关重要。这些结果表明，Müller 胶质细胞内局部视网膜生物钟在与年龄相关的视网膜疾病和视网膜变性中可能具有潜在作用。
