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HMG-CoA还原酶在人眼睑组织及人睑板腺上皮细胞系中的表达。

HMG-CoA reductase expression in human eyelid tissue and in a human meibomian gland epithelial cell line.

作者信息

Ooi Kenneth G-J, Rao Anupam, Goh Jonathan S-K, Gracie Gary, Cherepanoff Svetlana, Madigan Michele C, Watson Stephanie L

机构信息

Save Sight Institute, University of Sydney, Sydney Eye Hospital Campus, 8 Macquarie Street, Sydney, NSW, 2000, Australia.

University of Sydney, Sydney, 2006, Australia.

出版信息

Graefes Arch Clin Exp Ophthalmol. 2019 Apr;257(4):785-790. doi: 10.1007/s00417-019-04247-9. Epub 2019 Jan 21.

Abstract

PURPOSE

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

目的

3-羟基-3-甲基戊二酰辅酶A还原酶(HMGCR)是胆固醇生成的限速酶,已发现其有助于皮肤皮脂腺和毛囊的脂质分泌。我们使用免疫组织化学方法评估了HMGCR在人眼睑组织和永生化人睑板腺上皮细胞(HMGECs)中的表达。

方法

获取存档石蜡块中的全层人眼睑标本。每个蜡块切取的切片用苏木精和伊红染色,由眼科病理学家检查以验证组织病理学。使用Ventana自动染色系统,在连续切片上用兔抗人HMGCR抗体进行免疫组织化学。通过荧光免疫细胞化学和共聚焦显微镜检查HMGCR在HMEGCs中的表达。

结果

13个全层眼睑标本符合纳入标准。所有标本均含有睑板腺;2个(15%)含有蔡氏腺;3个(23%)含有皮脂腺;2个(15%)含有副泪腺;2个(15%)含有莫尔腺(睑缘腺)。免疫组织化学显示,所有标本中睑板腺的睑板细胞以及蔡氏腺和皮脂腺的皮脂细胞中均有HMGCR表达。HMGCR在血管内皮中也有明显表达;HMGCR在HMGEC细胞上的免疫荧光呈阳性。阴性Ig对照未见标记。

结论

HMGCR在所有眼睑皮脂腺类型腺体以及HMGECs中均有表达,这与胆固醇生成在泪膜脂质形成中的作用一致。观察到HMGCR的表达也为在睑缘炎等睑脂分泌异常的情况下,使用HMGCR抑制剂局部他汀类药物作为新型泪膜脂质稳定剂提供了理论依据

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