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Can Tetracycline Antibiotics Duplicate the Ability of Azithromycin to Stimulate Human Meibomian Gland Epithelial Cell Differentiation?

Liu, Yang MD; Kam, Wendy R. MS; Ding, Juan PhD; Sullivan, David A. PhD

doi: 10.1097/ICO.0000000000000351
Basic Investigation
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Purpose: Azithromycin and tetracyclines are commonly prescribed in the United States for the treatment of meibomian gland dysfunction (MGD). The efficacy of these antibiotics has been believed to be their antiinflammatory and antibacterial actions, which suppress MGD-associated posterior blepharitis and growth of lid bacteria. However, we recently discovered that azithromycin can act directly on human meibomian gland epithelial cells (HMGECs) to stimulate their function. In this study, we sought to determine whether tetracycline antibiotics can duplicate this azithromycin effect.

Methods: Immortalized HMGEC were cultured in the presence of a vehicle, azithromycin, doxycycline, minocycline, or tetracycline for 5 days. Cells were evaluated for cholesterol and neutral lipid staining, and the lipid composition of cellular lysates was analyzed by high-performance thin-layer chromatography.

Results: Our results demonstrate that azithromycin's ability to stimulate the differentiation of human meibomian gland cells is unique, and is not duplicated by doxycycline, minocycline, or tetracycline. Azithromycin, but not the other antibiotics, significantly increased the cellular accumulation of cholesterol, cholesterol esters, phospholipids, and lysosomes. These differentiative actions of azithromycin were paralleled by an increased expression of sterol regulatory element–binding protein 1.

Conclusions: Our findings show that the stimulatory effects of azithromycin on HMGEC function are unique and are not duplicated by the antibiotics doxycycline, minocycline, or tetracycline. Our results further suggest that this stimulatory influence of azithromycin may contribute to its beneficial effect in treating MGD and its associated evaporative dry eye disease.

Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, and Harvard Medical School, Boston, MA.

Reprints: Yang Liu, MD, Schepens Eye Research Institute, 20 Staniford St, Boston, MA 02114 (e-mail: yang_liu@meei.harvard.edu).

Supported by NIH grant EY05612, the Margaret S. Sinon Scholar in Ocular Surface Research Fund, and the Guoxing Yao Research Fund.

The authors have no conflicts of interest to disclose.

Yang Liu had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analyses.

A provisional patent has been filed around this technology. Intellectual property for this application is owned by the Schepens Eye Research Institute/Massachusetts Eye and Ear.

Received September 12, 2014

Received in revised form October 09, 2014

Accepted November 14, 2014

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