Hyperlipidemia induces Meibomian gland dysfunction

Abstract

AbstractPurposeTo investigate the pathological changes of meibomian gland (MG) and ocular surface tissues in Apolipoprotein E knockout (ApoE‐/‐) mice and wild type mice fed with high fat diet, and to illustrate the effect of hyperlipidemia on meibomian gland function.MethodsThe ocular surface of ApoE‐/‐ male mice and age and sex matched wild type mice fed with standard diet or high fat diet was observed under slit lamp microscope. MG tissue sections underwent H&E staining, Oil Red O staining, TUNEL assay, and immuno‐fluorescence staining for K10, Fabp5, Ki67, K6a, p63, PPAR‐g, NF‐kB p65, p‐NF‐kB p65, caspase 3, caspase 8, and immune‐histochemical staining for CD45. Real‐time RT‐PCR and Western blot was performed to detect above mentioned gene expression in MG tissues. Lipid metabolism related genes expression in MG were also detected by real‐time RT‐PCR.ResultsEyelid thickening, keratinization and corneal neovascularization occurred in ApoE‐/‐ mice at the age of 5 months, and the changes were more obvious at 7 months. H&E staining showed hypertrophy of the meibomian gland acinus, and Oil red O staining showed accumulation of lipid in MG acinus of ApoE‐/‐ mice. Both K10 and Fabp5 expression were increased, while Ki67, K6a, p63 were decreased in ApoE‐/‐ mice compared to the wild type mice. Cytoplasmic and nuclear expression of PPAR‐g was decreased, NF‐kB p65, p‐NF‐kB p65, caspase 3, and caspase 8 expression was higher in the ApoE‐/‐ mice compared to the wild type mice. TUNEL assay showed more positive cells in the meibomian gland acinus of ApoE‐/‐ mice. CD45 positive cell infiltration increased from 5 months to 7 months in ApoE‐/‐ mice. Lipid metabolism related genes such as FFAR1, PAR3, ACSL3, and LIPC were decreased in ApoE‐/‐ mice compared to the wild type mice. Wild type mice fed with high fat diet showed similar pathological changes as ApoE‐/‐ mice.ConclusionHyperlipidemia could induce abnormal meibomian gland acinar cell proliferation, differentiation, and lipid metabolism. Hyperlipidemia condition may be an important pathogenesis factor of meibomian gland dysfunction.