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Yi Zhang, Wendy Kam, David A Sullivan; Influence of pilocarpine and timolol on human meibomian gland epithelial cells.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5707.
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© ARVO (1962-2015); The Authors (2016-present)
Recently, investigators have discovered that topical anti-glaucoma drugs may induce meibomian gland dysfunction. This response may contribute to the decreased tear volume, tear film instability, posterior blepharitis, loss of visual acuity and symptoms of ocular burning, stinging, discomfort, redness, photophobia and foreign-body sensation commonly found in glaucoma patients taking such medications. We hypothesize that the action of these drugs may involve a direct effect on human meibomian gland epithelial cells (HMGECs). To begin to test this hypothesis, we examined the influence of the antiglaucoma drugs, pilocarpine and timlolol, on the morphology and survival of HMGECs.
Immortalized (I) HMGECs were cultured in keratinocyte serum-free media containing vehicle, pilocarpine (4.0 or 0.4%) or timolol (0.5 or 0.05%) for up to 24 hours. Experiments were repeated at least three times, and included positive controls for proliferation (epidermal growth factor and bovine pituitary extract). Cell counts were enumerated with a hemocytometer, cellular morphology was examined with a phase-contrast microscope, and statistics were performed with a one-way ANOVA.
The cholinergic agonist, pilocarpine, caused a dose-dependent decrease in the survival of IHMGECs. The 4.0% concentration, which is used clinically, was toxic and led to the death of most cells. Exposure to 0.4% pilocarpine resulted in a significant decrease in the proliferation of IHMGECs, as compared to controls. A reduction in cell number was also found following treatment with 0.5% (clinical dose), but not 0.05%, timolol, a beta-adrenergic receptor antagonist. Morphologically, 4.0% pilocarpine induced cellular atrophy within 3 hours. The 0.4% pilocarpine stimulated the accumulation of perinuclear vesicles after 3 hours of exposure, and this vacuolation appeared to increase both in number and size during the experimental time course. IHMGECs treated with 0.5% timolol exhibited cell shrinkage, rounding and poor adherence by 24 hours, whereas the 0.05% dose had minimal morphological effects.
Our results support our hypothesis and demonstrate that these antiglaucoma drugs, pilocarpine and timolol, have direct effects on HMGECs that may influence their morphology and survival.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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