中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (2): 207-210.doi: 10.4103/1673-5374.226383

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

血脂异常调节周围信息的神经胶质感应和转导

  

  • 收稿日期:2018-01-24 出版日期:2018-02-15 发布日期:2018-02-15

Dyslipidemia modulates Müller glial sensing and transduction of ambient information

Monika Lakk1, *, Felix Vazquez-Chona1, Oleg Yarishkin1, David Križaj1, 2, 3   

  1. 1 Department of Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, UT, USA
    2 Department of Bioengineering, University of Utah, Salt Lake City, UT, USA
    3 Department of Neurobiology & Anatomy, University of Utah, Salt Lake City, UT, USA
  • Received:2018-01-24 Online:2018-02-15 Published:2018-02-15
  • Contact: Monika Lakk, Ph.D.,mlakk@gamma.ttk.pte.hu.
  • Supported by:

    This study was supported by the NIH (R01EY022076, R01EY027920; P30EY014800), the Willard Eccles Foundation, Glaucoma Research Foundation, the Diabetes and Metabolism Center at the University of Utah and unrestricted support from Research to Prevent Blindness to the Moran Eye Institute at the University of Utah, USA.

摘要:

orcid:0000-0001-5660-2623(Monika Lakk)

Abstract:

Unesterified cholesterol controls the fluidity, permeability and electrical properties of eukaryotic cell membranes. Consequently, cholesterol levels in the retina and the brain are tightly regulated whereas depletion or oversupply caused by diet or heredity contribute to neurodegenerative diseases and vision loss. Astroglia, which play a central role in the biosynthesis, uptake and transport of cholesterol but also drive inflammatory signaling under hypercholesterolemic conditions associated with high-fat diet (diabetes) and neurodegenerative disease. A growing body of evidence shows that unesterified membrane cholesterol modulates the ability of glia to sense and transduce ambient information. Cholesterol-dependence of Muller glia - the retinal sentinels for metabolic, mechanical, osmotic and inflammatory signals - is mediated in part by transient receptor potential V4 (TRPV4) channels. Cholesterol supplementation facilitates whereas depletion suppresses TRPV4-mediated transduction of temperature and lipid agonists. However, it has less effect on the glial response to swelling. The acute effects of cholesterol supplementation/depletion on plasma membrane ion channels and calcium homeostasis differ from the effects of chronic dyslipidemia, possibly due to differential modulation of modality-dependent energy barriers associated with the functionality of polymodal channels embedded within lipid rafts. Understanding of cholesterol-dependence of TRP channels is thus providing insight into dyslipidemic pathologies associated with diabetic retinopathy, glaucoma and macular degeneration.

Key words: dyslipidemia, cholesterol, Müller glia, transient receptor potential V4, cyclodextrin, calcium, retina