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J.–M. Warnet, M. Dutot, C. Baudouin, P. Rat; Preservatives and P2X7 Cell Death Receptor Activation: Role in Iatrogenic Ocular Pathologies . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4945.
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Preservatives are known in ophthalmology to induce severe side effects. The aim of this work was to investigate the role of multipurpose solutions used to disinfect contact lens and the role of benzalkonium chloride preservative in P2X7 receptor–induced apoptosis on ocular surface.
Chang conjunctival cells were incubated with four multipurpose solutions and different benzalkonium chloride concentrations. Microplate cold light cytofluorometry and inverted fluorescence microscopy were performed to evaluate cell viability (neutral red test), reactive oxygen species (ROS) production (dichlorofluorescein diacetate and hydroethidine tests) and P2X7 cell death purinoreceptor activation (YO–PRO–1 test). P2X7 receptor presence on Chang cells was confirmed by immunohistochemistry.
Benzalkonium chloride was found to be the most cytotoxic preservative: as soon as 15 minutes of incubation, it induced necrosis with ROS overproduction. Even at very low concentrations, multipurpose solutions containing PHMB or polyquad preservatives were found to be apoptotic with mitochondria–dependent oxidative stress.
Benzalkonium chloride is used to preserve eye drops; when the active principle already presents antibacterial activity (such as fluoroquinolone), preservative should be avoided. Multipurpose solutions can induce side effects (dry eye for example) because of their preservatives which are cytotoxic: contact lens should be rinse with an inert solution after disinfection step.
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