June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
The effect of solithromycin, a cationic amphiphilic drug, on the proliferation and differentiation of human meibomian gland epithelial cells.
Author Affiliations & Notes
  • Yang Liu
    Schepens Eye Research Inst, Boston, Massachusetts, United States
  • Wendy R Kam
    Schepens Eye Research Inst, Boston, Massachusetts, United States
  • Prabhavathi Fernandes
    Cempra Pharmaceuticals, Chapel Hill, North Carolina, United States
  • David A Sullivan
    Schepens Eye Research Inst, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Yang Liu, Cempra Inc. (F); Wendy Kam, Cempra Inc. (F); Prabhavathi Fernandes, Cempra Inc. (E), Cempra Inc. (P); David Sullivan, Cempra Inc. (F)
  • Footnotes
    Support  Sponsored by Cempra Pharmaceuticals
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4379. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      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.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : 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.

Methods : 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).

Results : 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.

Conclusions : 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.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×