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Is P2X7 a potential therapeutic target in the treatment of retinal diseases: an animal study
Poster Abstracts
Is P2X7 a potential therapeutic target in the treatment of retinal diseases: an animal study Emily Shao, Shenzhen Tempest-Roe, Frederick Tam, Simon Taylor
Abstract Background Age-related macular degeneration and diabetic retinopathy are the two commonest causes of blindness in the UK and can be regarded as inflammatory diseases of ageing. The P2X7 receptor is thought to play a part in the development of such autoinflammatory conditions, and might be a potential therapeutic target, but its role in ocular inflammation is unknown. The aim of this study was to explore a mouse model of ocular inflammation. Methods Experimental autoimmune uveitis (EAU) was induced in P2X7–/– and wild-type (WT) mice to test whether P2X7 deficiency could prevent disease induction. Established EAU in B10rIII mice was treated with the P2X7 receptor antagonist A439079 or vehicle to see whether P2X7 blockade was effective in treating disease. Disease activity was observed with endoscopic retinal imaging until animals were culled at day 16. Findings P2X7 deficiency protected against the development of EAU, with mean disease scores significantly lower in P2X7–/– mice than in control WT mice (n=8, 12 [SD 4] vs n=9, 18 [4]; p=0·03). A439079 also effectively treated established EAU with disease scores in A439079-treated animals significantly lower than in vehicle-treated animals (n=12, 17 [11] vs n=10, 29 [10]; p=0·01).
Published Online February 25, 2016 Poster 73 Imperial College London, London, UK (E Shao BSc, S Tempest-Roe MSc, F Tam PhD); and University of Surrey, Guildford, UK (Prof S Taylor PhD) Correspondence to: Dr Emily Shao, Department of Ophthalmology, Imperial College London, Commonwealth Building, Hammersmith Campus, London W12 0NN, UK [email protected]
Interpretation Our findings show that P2X7 deficiency can protect against the development of a model of intraocular inflammation in mice and, importantly, that P2X7 antagonists can ameliorate established disease. The P2X7 receptor could be a viable therapeutic target for retinal diseases with an inflammatory pathogenesis; therefore, further studies in other disease models are justified. Funding Biotechnology and Biological Sciences Research Council, GlaxoSmithKline, Novartis. Contributors ES and ST-R did the experiments. ES wrote the abstract. FT provided advice about experiments. ST had the idea for the study, helped with experiments, and reviewed the abstract. Declaration of interests We declare no competing interests.
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Is P2X7 a potential therapeutic target in the treatment of retinal diseases: an animal study Emily Shao, Shenzhen Tempest-Roe, Frederick Tam, Simon Taylor
Abstract Background Age-related macular degeneration and diabetic retinopathy are the two commonest causes of blindness in the UK and can be regarded as inflammatory diseases of ageing. The P2X7 receptor is thought to play a part in the development of such autoinflammatory conditions, and might be a potential therapeutic target, but its role in ocular inflammation is unknown. The aim of this study was to explore a mouse model of ocular inflammation. Methods Experimental autoimmune uveitis (EAU) was induced in P2X7–/– and wild-type (WT) mice to test whether P2X7 deficiency could prevent disease induction. Established EAU in B10rIII mice was treated with the P2X7 receptor antagonist A439079 or vehicle to see whether P2X7 blockade was effective in treating disease. Disease activity was observed with endoscopic retinal imaging until animals were culled at day 16. Findings P2X7 deficiency protected against the development of EAU, with mean disease scores significantly lower in P2X7–/– mice than in control WT mice (n=8, 12 [SD 4] vs n=9, 18 [4]; p=0·03). A439079 also effectively treated established EAU with disease scores in A439079-treated animals significantly lower than in vehicle-treated animals (n=12, 17 [11] vs n=10, 29 [10]; p=0·01).
Published Online February 25, 2016 Poster 73 Imperial College London, London, UK (E Shao BSc, S Tempest-Roe MSc, F Tam PhD); and University of Surrey, Guildford, UK (Prof S Taylor PhD) Correspondence to: Dr Emily Shao, Department of Ophthalmology, Imperial College London, Commonwealth Building, Hammersmith Campus, London W12 0NN, UK [email protected]
Interpretation Our findings show that P2X7 deficiency can protect against the development of a model of intraocular inflammation in mice and, importantly, that P2X7 antagonists can ameliorate established disease. The P2X7 receptor could be a viable therapeutic target for retinal diseases with an inflammatory pathogenesis; therefore, further studies in other disease models are justified. Funding Biotechnology and Biological Sciences Research Council, GlaxoSmithKline, Novartis. Contributors ES and ST-R did the experiments. ES wrote the abstract. FT provided advice about experiments. ST had the idea for the study, helped with experiments, and reviewed the abstract. Declaration of interests We declare no competing interests.
www.thelancet.com
91