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Simon Richard Taylor, Shenzhen Tempest-Roe, Emily Shao, John McDaid; P2X7 Deficiency Protects Against Experimental Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2501.
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The immune system is designed to discriminate between self and non-self, but also to detect foreign antigens in the context of ‘danger’. It has been suggested that ATP provides such a stimulus, acting via the purinergic P2X7 receptor, and that pathological stimulation of the P2X7 receptor may be involved in the development of autoimmune disease. We therefore explored the impact of P2X7 deficiency on the development of Experimental Autoimmune Uveitis (EAU) in mice, to whether this receptor may be a viable therapeutic target.
EAU was induced in two strains of P2X7-/- mice (which were both generated on a C57BL/6 background) and in C57BL/6 control animals, using 500 µg IRBP peptide 1-20 (GPTHLFQPSLVLDMAKVLLD) in PBS emulsified in CFA. Additional adjuvant of 1.5 µg Bordetella pertussis toxin was injected into the peritoneal cavity. Procedures were performed under a Home Office License in accordance with the regulations of the United Kingdom Animal (Scientific Procedures) Act (1986). Animals were monitored using topical endoscopic fundal imaging and culled at day 28, when histological examination of eyes was undertaken.
P2X7 deficiency protected against the development of EAU, with disease scores being significantly lower in both strains of gene-targeted animals compared to control animals (Figure 1). There were also differences in disease scores between the two strains of gene-targeted animals, with Pfizer P2X7-/- showing lower disease activity scores than GlaxoSmithKline P2X7-/- animals.
P2X7 deficiency protects against the development of EAU in mice and may represent a viable therapeutic target for ocular inflammatory disease. Intra-strain differences may reflect the differences in gene targeting approaches and selective deletion (or failure of deletion) of splice variants.
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