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M. Dutot, H. Liang, F. Brignole-Baudouin, C. Baudouin, J.-M. Warnet, P. Rat; P2X7 Cell Death Receptor Implication in Ocular Toxicology. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4189.
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© ARVO (1962-2015); The Authors (2016-present)
P2X7 receptor is a ligand-gated ion channel activated by extracellular ATP. Repeated or prolonged application of agonist induces the formation of a cytolytic pore. P2X7 receptor has been studied in neuronal degenerative pathologies (Alzheimer) and in rheumatoid arthritis. The aim of this study was to localize P2X7 receptor in different ocular cell lines and to identify its role in different ocular stress.
Immunohistochemistry was performed on Chang conjunctival cell line, HCE-T cell line (human cornea), ARPE-19 cell line (human retina) cells and SRA01/04 cell line (human lens) to localize P2X7 receptor protein using extracellular antibody.YO-PRO-1 dye uptake was used to confirm the activity of P2X7 receptor after stimulation with two agonists (ATP and BzATP). Cells were incubated with either benzalkonium chloride (BAC) or tert-Butyl HydroPeroxide (tBHP). P2X7 receptor activation was then evaluated using the YO-PRO-1 test.
The four cell lines expressed P2X7 receptor. BzATP, a more potent P2X7 agonist than ATP, induced higher YO-PRO-1 uptake (increased fluorescence signal). BAC increased YO-PRO-1 signal on both corneal and conjunctival cells, with maximum at 0.05% (corneal cells) and 0.02% (conjunctival cells) BAC concentrations.tBHP, a reactive oxygen species (ROS) inducer, stimulated P2X7 receptor activation on retinal cells.
P2X7 receptor is expressed in ocular tissues and is implicated in ocular surface iatrogenic pathologies (BAC toxicity). Retina is at risk for oxidative damage, and since P2X7 receptor seems to be activated by ROS, this receptor could be an interesting target to cure or avoid many ocular diseases.
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