Abstract：
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 retina are known to express the circadian clock in rodents; however, retinal clock expression in the human has not previously been localized. Moreover, the effect of local circadian clock dysfunction on retinal homeostasis is incompletely understood. We demonstrate an age-dependent decline in circadian clock gene and protein expression in the human retina. Using an animal model of targeted Bmal1 deficiency, we 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.
摘要：
整个身体的生物过程是通过调节当地的生物钟来及时协调的。视网膜是代谢最活跃的组织之一，与需求很大程度上取决于光/暗周期。已知视网膜内的大多数细胞类型在啮齿动物中表达昼夜节律,然而,视网膜时钟在人类中的表达以前没有被定位。此外，局部昼夜节律时钟功能障碍对视网膜稳态的影响尚不完全清楚。我们证明了人类视网膜中昼夜节律基因和蛋白质表达的年龄依赖性下降。使用靶向Bmal1缺乏症的动物模型，我们确定视网膜穆勒神经胶质的昼夜节律是神经元存活所必需的，血管完整性,和视网膜功能。这些结果表明，Müller胶质细胞内的局部视网膜昼夜节律在与年龄相关的视网膜疾病和视网膜变性中的潜在作用。
