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David A Sullivan, Yang Liu, Juan Ding, Wendy R Kam; Do cyclosporine A, anakinra, uridine triphosphate, rebamipide or bimatoprost influence the proliferation, differentiation or signaling of human meibomian gland epithelial cells?. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2504.
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© ARVO (1962-2015); The Authors (2016-present)
Researchers have hypothesized that treatment with cyclosporine A (CyA), interleukin-1 receptor antagonists (e.g. anakinra), P2Y2 receptor agonists (e.g. uridine triphosphate; UTP) and rebamipide may alleviate human meibomian gland dysfunction (MGD) and/or dry eye disease. Investigators have also proposed that prostaglandin analogues (e.g. bimatoprost) may induce MGD. Our goal was to determine whether these compounds directly influence human meibomian gland epithelial cell (HMGEC) function.
Multiple concentrations of each compound were tested for effects on immortalized (I) HMGEC morphology and survival. Non-toxic dosages were used for our studies. IHMGEC were cultured in the presence of vehicle, CyA (8 nM), anakinra (10 µg/ml), UTP (100 µM), rebamipide (1 nM) or bimatoprost (10 µM) for up to 6 days in various media. Experiments were repeated at least twice, and included positive controls for proliferation (epidermal growth factor and bovine pituitary extract), differentiation (azithromycin) and signaling pathways (insulin-like growth factor 1). Cells were analyzed for neutral lipid staining (LipidTox), lysosome accumulation (LysoTracker), lipid composition (high performance thin-layer chromatography) and AKT phosphorylation.
Our findings demonstrate that CyA, anakinra, UTP, rebamipide and bimatoprost had no effect on the proliferation, neutral lipid content, lysosome number, or levels of free cholesterol, triglycerides or phospholipids in IHMGEC. CyA, anakinra, rebamipide and bimatoprost significantly reduced the phosphorylation of AKT, as compared to control. Of interest, tested doses of CyA above 8 nM (i.e. 10 nM and 0.5 µM) killed the IHMGEC.
Our results show that CyA, anakinra, UTP, rebamipide and bimatoprost do not influence the proliferation or differentiation of IHMGEC. However, with the exception of UTP, these compounds do decrease the activity of the AKT signaling pathway, which is known to promote cell survival.
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