Dyslipidemia modulates Müller glial sensing and transduction of ambient information
Monika Lakk
Felix Vazquez-Chona
Oleg Yarishkin
David Kri?aj
摘要：Unesterified cholesterol controls the fluidity, permeability and electrical properties of eukaryotic cell mem-branes. 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. Astrog-lia play a central role in the biosynthesis, uptake and transport of cholesterol and also drive inflammatory signaling under hypercholesterolemic conditions associated with high-fat diet (diabetes) and neurodegen-erative 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 Müller glia - which function as retinal sentinels for metabolic, mechanical, osmotic and inflammatory signals - is mediated in part by transient receptor potential V4 (TRPV4) channels. Cholesterol supplementation facilitates, where-as depletion suppresses, TRPV4-mediated transduction of temperature and lipid agonists in Müller cells. Acute effects of cholesterol supplementation/depletion on plasma membrane ion channels and calcium ho-meostasis differ markedly 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.
机标关键词：
资助基金：This study was supported by the NIH(R01EY022076)This study was supported by the NIH(R01EY027920)This study was supported by the NIH(P30EY014800)
论文发表日期：2018-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：4( 207-210 )
英文信息