Hyperlipidemia induces meibomian gland dysfunction

Jinghua Bu; Yang Wu; Xiaoxin Cai; Nan Jiang; M Vimalin Jeyalatha; Jingwen Yu; Xin He; Hui He; Yuli Guo; Mingjie Zhang; Andrew J Quantock; Zuguo Liu; Wei Li

doi:10.1016/j.jtos.2019.06.002

Hyperlipidemia induces meibomian gland dysfunction

Ocul Surf. 2019 Oct;17(4):777-786. doi: 10.1016/j.jtos.2019.06.002. Epub 2019 Jun 13.

Authors

Jinghua Bu¹, Yang Wu¹, Xiaoxin Cai¹, Nan Jiang¹, M Vimalin Jeyalatha¹, Jingwen Yu¹, Xin He¹, Hui He¹, Yuli Guo¹, Mingjie Zhang¹, Andrew J Quantock², Zuguo Liu¹, Wei Li³

Affiliations

¹ Department of Ophthalmology, Xiang'an Hospital of Xiamen University; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science; Eye Institute of Xiamen University; School of Medicine, Xiamen University, China.
² School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK.
³ Department of Ophthalmology, Xiang'an Hospital of Xiamen University; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science; Eye Institute of Xiamen University; School of Medicine, Xiamen University, China. Electronic address: wei1018@xmu.edu.cn.

PMID: 31201956
DOI: 10.1016/j.jtos.2019.06.002

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.

Keywords: Apolipoprotein E; Hyperlipidemia; Inflammation; Meibomian gland dysfunction; PPAR-γ.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apolipoproteins E / biosynthesis
Apolipoproteins E / blood
Apolipoproteins E / genetics*
Blotting, Western
Disease Models, Animal
Gene Expression Regulation*
Hyperlipidemias / complications*
Hyperlipidemias / metabolism
Male
Meibomian Gland Dysfunction / diagnosis
Meibomian Gland Dysfunction / etiology*
Meibomian Gland Dysfunction / metabolism
Meibomian Glands / metabolism
Meibomian Glands / pathology*
Mice
Mice, Knockout
RNA / genetics*
Rabbits

Substances

Apolipoproteins E
RNA