This is still an incomplete list, but I wanted to post about the well known toxins to the meibomian glands and what I know to date.
Which Drops & Drugs That Destroy Meibomian Glands?
1. Accutane: this is well know to damage meibomian glands
2. Pilocarpine: used for glaucoma, study below (Reference 1) are concerned this drug damages meibomian gland cells.
3. Timolol: used for glaucoma, study below (Reference 1) are concerned this drug damages meibomian gland cells.
Which Drops & Drugs That Help Meibomian Glands?
2. Omega 3
Which Drops/Drugs that Appear to Have “No Effect” on Meibomian Glands? (Reference 2)
1. cyclosporine A (CyA),
2. interleukin-1 receptor antagonists (IL-1RA; e.g., anakinra),
3. P2Y2 receptor agonists (e.g., uridine triphosphate; UTP), and
4. rebamipide may alleviate human meibomian gland dysfunction (MGD) and/or dry eye disease.
5. prostaglandin analogues (e.g., bimatoprost or Alphagan): appear not to hurt Meibomian Glands
References:1. Summary: pilocarpine and timolol cause a dose-dependent decrease in IHMGEC (eg., Meibomian Gland cell) survival. The topical concentrations of these drugs used clinically are toxic and lead to cell atrophy, poor adherence, or death. By contrast, drug levels equivalent to those that reportedly appear within the palpebral conjunctiva after topical application do not influence IHMGEC survival. These latter levels also have no effect on IHMGEC proliferation or differentiation and do not interfere with the ability of AZM to stimulate cellular neutral lipid and lysosome accumulation. The 0.001% dose of pilocarpine, though, does suppress the EGF+BPE-induced proliferation of IHMGECs. Overall, our results support our hypothesis and demonstrate that the antiglaucoma drugs, pilocarpine and timolol, have direct effects on HMGECs, which may affect their morphology, survival, and proliferative capacity.Cornea Influence of Pilocarpine and Timolol on Human Meibomian Gland Epithelial CellsZhang, Yi MD*,†; Kam, Wendy R. MS†; Liu, Yang MD†; Chen, Xiaomin MD, PhD†; Sullivan, David A. MS, PhD, FARVO†firstname.lastname@example.org).
Purpose: Investigators have discovered that topical antiglaucoma drugs may induce meibomian gland dysfunction. This response may contribute to the dry eye disease commonly found in patients with glaucoma taking such medications. We hypothesize that drug action involves a direct effect on human meibomian gland epithelial cells (HMGECs). To test this hypothesis, we examined the influence of the antiglaucoma drugs, pilocarpine and timolol, on the morphology, survival, proliferation, and differentiation of HMGECs.
Methods: Immortalized (I) HMGECs (n = 2–3 wells/treatment/experiment) were cultured with multiple concentrations of pilocarpine or timolol for up to 7 days. Experiments included positive controls for proliferation (epidermal growth factor and bovine pituitary extract) and differentiation (azithromycin). Cells were enumerated using a hemocytometer and evaluated for morphology, neutral lipid staining, and lysosome accumulation.
Results: Our results demonstrate that pilocarpine and timolol cause a dose-dependent decrease in the survival of IHMGECs. The clinically used concentrations are toxic and lead to cell atrophy, poor adherence, or death. By contrast, drug levels that are known to accumulate within the conjunctiva, adjacent to the meibomian glands, do not influence IHMGEC survival. These latter concentrations also have no effect on IHMGEC proliferation or differentiation, and they do not interfere with the ability of azithromycin to stimulate cellular neutral lipid and lysosome accumulation. This dose of pilocarpine, though, did suppress the epidermal growth factor+bovine pituitary extract–induced proliferation of IHMGECs.
Conclusions: Our results support our hypothesis and demonstrate that these antiglaucoma drugs, pilocarpine and timolol, have direct effects on HMGECs that may influence their morphology, survival, and proliferative capacity.
2. Invest Ophthalmol Vis Sci. 2016 Aug 1;57(10):4287-94. doi: 10.1167/iovs.16-19937.
Do Cyclosporine A, an IL-1 Receptor Antagonist, Uridine Triphosphate, Rebamipide, and/or Bimatoprost Regulate Human Meibomian Gland Epithelial Cells?
Researchers have hypothesized that treatment with cyclosporine A (CyA), interleukin-1 receptor antagonists (IL-1RA; 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. Nontoxic dosages were used for our studies. Immortalized HMGEC were cultured in the presence of vehicle, CyA, IL-1RA, UTP, rebamipide, or bimatoprost for up to 6 days in various media. Experiments included positive controls for proliferation (epidermal growth factor and bovine pituitary extract), differentiation (azithromycin), and signaling pathway activation (insulin-like growth factor 1). Cells were analyzed for neutral lipid staining, lysosome accumulation, lipid composition, and phosphatidylinositol-3-kinase/Akt (AKT), phosphorylation.
Our findings demonstrate that CyA, IL-1RA, UTP, rebamipide, and bimatoprost had no effect on the proliferation; neutral lipid content; lysosome number; or levels of free cholesterol, triglycerides, or phospholipids in IHMGECs. Cylosporine A, IL-1RA, rebamipide, and bimatoprost significantly reduced the phosphorylation of AKT, as compared to control. Of interest, tested doses of CyA above 8 nM killed the IHMGECs.
Our results show that CyA, IL-1RA, 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.
prostaglandin analogues (e.g., bimatoprost or Alphagan): appear not to hurt Meibomian Glands
*Department of Ophthalmology, Western China Hospital, Sichuan University, Sichuan, China; and
†Department of Ophthalmology, Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA.
Reprints: David A. Sullivan, MS, PhD, FARVO, Schepens Eye Research Institute, 20 Staniford St, Boston, MA 02114 (e-mail:
Supported by NIH grant R01EY05612, the Margaret S. Sinon Scholar in Ocular Surface Research Fund, the Chinese Scholar Council, and the Guoxing Yao Research Fund.
The authors have no conflicts of interest to disclose.
Received December 28, 2016
Received in revised form January 30, 2017
Accepted February 02, 2017