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Although one of the highest risk factors for glaucoma is elevated intraocular pressure (IOP) and reduction in IOP is the only proven treatment, the mechanism of IOP regulation is poorly understood. We report that the P2Y\n                    <jats:sub>6<\/jats:sub>\n                    receptor is critical for lowering IOP and that ablation of the P2Y\n                    <jats:sub>6<\/jats:sub>\n                    gene in mice (P2Y\n                    <jats:sub>6<\/jats:sub>\n                    KO) results in hypertensive glaucoma\u2013like optic neuropathy. Topically applied uridine diphosphate, an endogenous selective agonist for the P2Y\n                    <jats:sub>6<\/jats:sub>\n                    receptor, decreases IOP. The P2Y\n                    <jats:sub>6<\/jats:sub>\n                    receptor was expressed in nonpigmented epithelial cells of the ciliary body and controlled aqueous humor dynamics. P2Y\n                    <jats:sub>6<\/jats:sub>\n                    KO mice exhibited sustained elevation of IOP, age-dependent damage to the optic nerve, thinning of ganglion cell plus inner plexiform layers, and a reduction of RGC numbers. These changes in P2Y\n                    <jats:sub>6<\/jats:sub>\n                    KO mice were attenuated by an IOP lowering agent. Consistent with RGC damage, visual functions were impaired in middle-aged P2Y\n                    <jats:sub>6<\/jats:sub>\n                    KO mice. We also found that expression and function of P2Y\n                    <jats:sub>6<\/jats:sub>\n                    receptors in WT mice were significantly reduced by aging, another important risk factor for glaucoma. In summary, our data show that dysfunctional purinergic signaling causes IOP dysregulation, resulting in glaucomatous optic neuropathy.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.93456","type":"journal-article","created":{"date-parts":[[2017,10,4]],"date-time":"2017-10-04T11:00:45Z","timestamp":1507114845000},"source":"Crossref","is-referenced-by-count":23,"title":["Purinergic dysregulation causes hypertensive glaucoma\u2013like optic neuropathy"],"prefix":"10.1172","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6448-1304","authenticated-orcid":true,"given":"Youichi","family":"Shinozaki","sequence":"first","affiliation":[{"name":"Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Kashiwagi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, 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