HMG-CoA reductase expression in human eyelid tissue and in a human meibomian gland epithelial cell line
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3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), the rate-limiting enzyme of cholesterol production, has been found to contribute to lipid secretion from skin sebaceous glands and hair follicles. We assessed for HMGCR expression in human eyelid tissue and in immortalized human meibomian gland epithelial cells (HMGECs) using immunohistochemistry.
Full thickness human eyelid specimens in archival paraffin blocks were obtained. A section from each block was stained with hematoxylin and eosin and examined by an ocular pathologist for validation of tissue pathology. Immunohistochemistry was performed using rabbit anti-human HMGCR antibody on serial sections using the Ventana automated staining system. HMGCR expression was examined for in HMEGCs with fluorescence immunocytochemistry and confocal microscopy.
Thirteen full thickness eyelid specimens met the inclusion criteria. All specimens contained meibomian glands, and 2 (15%) contained glands of Zeis, 3 (23%) pilosebaceous glands, 2 (15%), accessory lacrimal glands, and 2 (15%), glands of Moll, respectively. Immunohistochemistry showed HMGCR expression in meibocytes of meibomian glands and sebocytes of Zeis and pilosebaceous glands in all specimens. HMGCR expression was also evident in vascular endothelium. Immunofluorescence was positive for HMGCR expression on HMGEC cells. No labeling was seen for the negative Ig control.
HMGCR was expressed in all eyelid sebaceous-type glands and in HMGECs, consistent with a role for cholesterol production in the genesis of tear film lipids. The observed expression also provides a rationale for using topical statins, inhibitors of HMGCR, as novel tear film lipid stabilizers in conditions such as blepharitis, where meibum production is aberrant.
KeywordsHMG-CoA reductase Statin Cholesterol Meibomian gland Blepharitis Dry eye Vascular endothelium
The immortalized human meibomian gland cell line was provided, with thanks, by Professor David Sullivan, Schepens Eye Research Institute, Boston, MA, USA.
Professor SL Watson is supported by a Sydney Medical School Foundation fellowship.
This research did not receive any specific grant from funding agencies in the public, commercial, or not for profit sectors.
Compliance with ethical standards
Conflict of interest
KGO and SLW have a patent on topical Atorvastatin as a novel tear film stabilizer.
The immunolabeling studies were approved by the South Eastern Sydney Local Health District Human Research Committee (HREC ref. no.: 13/359) and adhered to the Tenets of the Declaration of Helsinki.
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