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Hong Liang, Christophe Baudouin, Philippe Daull, Jean-Sebastien Garrigue, Francoise Brignole-Baudouin; Effects Of Prostaglandin Analogues Anti-glaucoma Therapies On Ocular Surface Mucins. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3559.
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© ARVO (1962-2015); The Authors (2016-present)
Ocular surface mucins are glycosylated proteins that have an important role in the lubrication and protection of the ocular mucosa. 60% of glaucoma patients have signs and symptoms of dry eye, a disease associated with mucin expression alterations. The aim of the present study was to evaluate the effects of prostaglandin analogues (PGA) anti-glaucoma therapies on mucins levels in a newly developed in vitro corneal wound-healing model.
A wound was created by mechanically scraping through a monolayer of confluent immortalized human corneal epithelial (HCE) cells. Wound closure was measured 2 hours (H) and 1-3 days (D) after a 30 min exposure to either: phosphate buffered saline (PBS), different concentrations of benzalkonium chloride (BAK; 0.0001% to 0.02%), latanoprost-0.02%BAK, travoprost-0.015%BAK, bimatoprost-0.005%BAK, tafluprost-0.01%BAK, BAK-free tafluprost, BAK-free latanoprost in Cationic Emulsion (LataCEm), Sofzia®-preserved and Polyquad®-preserved travoprost, diluted at 1:10. The percentages of wound closure were calculated at each time point. Immunohistology was performed for MUC1, MUC4, MUC16 and Ki-67 at D1.
The BAK dose-response curve confirmed the negative effect of BAK on HCE cells: decreased mucins levels and alteration of the wound healing process in a concentration-dependent manner. BAK-preserved PG analogues delayed HCE cells’ healing, and reduced the expression levels of MUC1, MUC4, and MUC16. They also decreased the number of Ki-67-positive proliferating cells. In contrast, BAK-free and soft-preserved PGAs up-regulated mucins, while maintaining Ki-67-positive cells. Interestingly, these BAK-free and soft-preserved PGAs improved mucins profiles when compared to PBS.
These data demonstrate the beneficial role of PGAs on the expression of ocular surface mucins, and the restoration of the ocular surface integrity. BAK, even at low concentrations, blocks the wound healing process. Moreover, BAK annihilates the positive effects of PGAs on mucins, possibly through pro-inflammatory action and detergent effect triggering mucus depletion; thus confirming the importance of BAK’s removal in anti-glaucoma eye drops. Preservative-free PGAs formulations, such as in cationic emulsion, that help maintaining the ocular surface integrity might be of particular interest for the management of glaucoma patients with or without OSD.
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