中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (11): 1861-1870.doi: 10.4103/1673-5374.239431

• 综述:视神经损伤修复保护与再生 •    下一篇

未折叠蛋白反应信号和视网膜Müller细胞代谢

  

  • 收稿日期:2018-07-20 出版日期:2018-11-15 发布日期:2018-11-15

The unfolded protein response signaling and retinal Müller cell metabolism

Kristen Kelly1, Joshua J. Wang1, 2, Sarah X. Zhang1, 2   

  1. 1 Department of Ophthalmology and Neuroscience Program, Ross Eye Institute, University at Buffalo, State University of New York, Buffalo, NY, USA
    2 SUNY Eye Institute, State University of New York, Buffalo, NY, USA
  • Received:2018-07-20 Online:2018-11-15 Published:2018-11-15
  • Contact: Sarah X. Zhang, PhD,xzhang38@buffalo.edu.
  • Supported by:

    This work is supported, in part, by NIH/NEI grants EY019949 and EY025061, and an Unrestricted Grant to the Department of Ophthalmology, SUNY-Buffalo, from Research to Prevent Blindness.

摘要:

 

orcid:0000-0002-7848-3263(Sarah X. Zhang)

Abstract:

The retina is one of the most energy demanding tissues in the body. Like most neurons in the central nervous system, retinal neurons consume high amounts of adenosine-5′-triphosphate (ATP) to generate visual signal and transmit the information to the brain. Disruptions in retinal metabolism can cause neuronal dysfunction and degeneration resulting in severe visual impairment and even blindness. The homeostasis of retinal metabolism is tightly controlled by multiple signaling pathways, such as the unfolded protein response (UPR), and the close interactions between retinal neurons and other retinal cell types including vascular cells and Müller glia. The UPR is a highly conserved adaptive cellular response and can be triggered by many physiological stressors and pathophysiological conditions. Activation of the UPR leads to changes in glycolytic rate, ATP production, de novo serine synthesis, and the hexosamine biosynthetic pathway, which are considered critical components of Müller glia metabolism and provide metabolic support to surrounding neurons. When these pathways are disrupted, neurodegeneration occurs rapidly. In this review, we summarize recent advance in studies of the UPR in Müller glia and highlight the potential role of the UPR in retinal degeneration through regulation of Müller glia metabolism.

Key words: unfolded protein response, retina, Müller glia, metabolism, neurodegeneration, X-box binding protein 1, glycolysis, glucose transporter