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Dyslipidemia modulates Müller glial sensing and transduction of ambient information

Neural Regeneration Research 2018年第2期13卷 207-210页

作者： Monika Lakk Felix Vazquez-Chona oleg yarishkin David Krizaj Department of Ophthalmology&Visual Sciences University of UtahSalt Lake CityUTUSA Department of Bioengineering University of UtahSalt Lake CityUTUSA Department of Neurobiology&Anatomy University of UtahSalt Lake CityUTUSA

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 Mfiller 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 Mfiller 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.

关键词： dyslipidemia cholesterol Muller glia transient receptor potential V4 cyclodextrin calcium retina

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