Hyperlipidemia induces meibomian gland dysfunction.

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.
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