Hyperlipidemia induces meibomian gland dysfunction

Bu, Jinghua, Wu, Yang, Cai, Xiaoxin, Jiang, Nan, Jeyalatha, M. Vimalin, Yu, Jingwen, He, Xin, He, Hui, Guo, Yuli, Zhang, Mingjie, Quantock, Andrew J. ORCID: https://orcid.org/0000-0002-2484-3120, Liu, Zuguo and Li, Wei 2019. Hyperlipidemia induces meibomian gland dysfunction. The Ocular Surface 17 (4) , pp. 777-786. 10.1016/j.jtos.2019.06.002

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Abstract

Purpose To investigate the pathological changes of the meibomian gland (MG) and ocular surface in Apolipoprotein E knockout (ApoE−/−) mice and to investigate the association of meibomian gland dysfunction (MGD) with hyperlipidemia. Methods Total plasma cholesterol was measured in different ages of ApoE−/− and wild type (WT) mice, whilst the ocular surfaces were observed by slit-lamp biomicroscopy. MG sections were subjected to H&E staining, Oil Red O staining, TUNEL assay and immunostaining. Quantitate RT-PCR and Western blot analyses were performed to detect the relative gene expression in MGs. The 5-month-old ApoE−/− mice were administered with rosiglitazone or GW9662 + rosiglitazone via oral gavage for 2 months to determine their effect on MG pathological change. Results We found eyelid abnormality, MG dropout, abnormal MG acinar morphology, dilated MG duct and plugging of the MG orifice in ApoE−/− mice. MG acini in ApoE−/− mice showed exaggerated lipid accumulation. Abnormal keratinization increased in MG duct, accompanied with decreased proliferation and increased apoptosis in ApoE−/− mice. Inflammatory cells infiltrated into the surrounding microenvironment of MG acini, and the NF-κB signaling pathway was activated in MG acinar cells. Oxidative stress was evident in MG acinar cells of ApoE−/− mice. Further investigation showed downregulation of PPAR-γ in MG acinar cells of ApoE−/− mice. PPAR-γ agonist rosiglitazone treatment reduced the morbidity of eyelid, as well as corneal pathological changes and MG inflammation in ApoE−/− mice. Conclusion MGD and hyperlipidemia are closely associated in ApoE−/− mice, which represent a new model to study the pathophysiology of MGD related to dyslipidemia.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Optometry and Vision Sciences
Publisher:	Elsevier
ISSN:	1542-0124
Date of Acceptance:	10 June 2019
Last Modified:	24 Feb 2023 11:45
URI:	https://orca.cardiff.ac.uk/id/eprint/157178

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