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Yang Liu, Wendy R Kam, Prabhavathi Fernandes, David A Sullivan; The effect of solithromycin, a cationic amphiphilic drug, on the proliferation and differentiation of human meibomian gland epithelial cells.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4379.
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© ARVO (1962-2015); The Authors (2016-present)
We have discovered that azithromycin (AZM) acts directly on immortalized human meibomian gland epithlelial cells (HMGECs) to stimulate their lysosome and lipid accumulation and overall differentiation. We hypothesize that this phospholipidosis-like effect of AZM on HMGECs is due to its cationic amphiphilic drug (CAD) nature. CADs feature a hydrophobic ring structure linked to a hydrophilic domain with a cationic amine group. If our hypothesis is correct, then other CADs (e.g. solithromycin [SOL]) should be able to duplicate AZM’s action on HMGECs. Our purpose was to test this hypothesis.
Immortalized HMGECs were cultured in the presence of vehicle or SOL (2, 10, or 20 µg/ml) for up to 7 days under proliferating (keratinocyte serum-free medium; KSFM) or differentiating (DMEM/F12 plus 10% fetal bovine serum) conditions. Positive (epidermal growth factor and bovine pituitary extract for proliferation; AZM for differentiation) and negative (media only) controls were included with the experiments. HMGECs were evaluated for cell number, neutral lipid content (LipidTox) and lysosome accumulation (LysoTracker).
Our results demonstrate that SOL induces a rapid and dose-dependent increase in the accumulation of neutral lipids and lysosomes in HMGECs. The lysosomal effects were most prominent with the 10 and 20 µg/ml doses, and occurred earlier (i.e. 1 day) with SOL than with the AZM (10 µg/ml) control. The effects of SOL and AZM on HMGEC differentiation were essentially the same after 3 days of culture. SOL did not influence the proliferation of HMGECs during a 7-day time period.
Our results support our hypothesis that SOL, a CAD, is able to duplicate, at least, AZM’s impact on lysosome and lipid accumulation, as well as differentiation, of HMGECs. The effect of SOL on lysosome appearance was faster than that of AZM.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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