Hyperlipidemia affects tight junctions and pump function in the corneal endothelium

Bu, Jinghua, Yu, Jingwen, Wu, Yang, Cai, Xiaoxin, Li, Kechun, Tang, Liying, Jiang, Nan, Jeyalatha, M. Vimalin, Zhang, Minjie, Sun, Huimin, He, Hui, Quantock, Andrew J. ORCID: https://orcid.org/0000-0002-2484-3120, Chen, Yongxiong, Liu, Zuguo and Li, Wei 2020. Hyperlipidemia affects tight junctions and pump function in the corneal endothelium. The American Journal of Pathology 190 (3) , pp. 563-576. 10.1016/j.ajpath.2019.11.008

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Abstract

Hyperlipidemia impacts on various diseases, such as atherosclerosis, hypertension, and diabetes mellitus. However, its influence, if any, on ocular tissues is largely unknown. Herein, we developed hyperlipidemic murine models by feeding 4-week–old male wild-type mice with a high-fat diet and apolipoprotein E knockout (ApoE−/−) mice with a high-fat diet or standard diet to investigate the corneal endothelial change under hyperlipidemic conditions. Oil Red O staining showed an accumulation of lipid droplets in corneal endothelial cells (CECs) of hyperlipidemic mice. Other manifestations included a reduced cell density and distorted cell morphology, a disruption of the endothelial cell tight junctions and adhesion junctions, a reduced number of surface microvilli, down-regulation of Na+-K+-ATPase expression and function, activation of oxidative stress, changes in mitochondrial ultrastructure, and increased apoptosis. CEC recovery after injury, moreover, was diminished in hyperlipidemic mice; and high palmitate levels were found in the aqueous humor. In vitro hyperlipemia model, moreover, was found to be associated with dose-dependent CEC cytotoxicity, altered cell morphology, reduced pump function, and an induction of oxidative stress, leading to functional and pathologic changes in the corneal endothelium.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Optometry and Vision Sciences
Publisher:	Elsevier
ISSN:	0002-9440
Date of Acceptance:	14 November 2019
Last Modified:	22 Feb 2023 14:15
URI:	https://orca.cardiff.ac.uk/id/eprint/157177

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