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The cAMP\u2010activated Cl2 channel cystic fibrosis transmembrane conductance regulator (CFTR) is a major prosecretory channel at the ocular surface. We investigated whether compounds that target CFTR can correct the abnormal tear film in dry eye. Small\u2010molecule activators of human wild\u2010type CFTR identified by high\u2010throughput screening were evaluated in cell culture and\n                    <jats:italic>in vivo<\/jats:italic>\n                    assays, to select compounds that stimulate Cl\n                    <jats:sup>\u2013<\/jats:sup>\n                    \u2010driven fluid secretion across the ocular surface in mice. An aminophenyl\u20101,3,5\u2010triazine, CFTR\n                    <jats:sub>act<\/jats:sub>\n                    \u2010K089, fully activated CFTR in cell cultures with EC\n                    <jats:sub>50<\/jats:sub>\n                    ~250 nM and produced an ~8.5 mV hyperpolarization in ocular surface potential difference. When delivered topically, CFTR\n                    <jats:sub>act<\/jats:sub>\n                    \u2010K089 doubled basal tear volume for 4 h and had no effect in CF mice. CFTR\n                    <jats:sub>act<\/jats:sub>\n                    \u2010K089 showed sustained tear film bioavailability without detectable systemic absorption. In a mouse model of aqueous\u2010deficient dry eye produced by lacrimal ablation, topical administration of 0.1 nmol CFTR\n                    <jats:sub>act<\/jats:sub>\n                    \u2010K089 3 times daily restored tear volume to basal levels, preventing corneal epithelial disruption when initiated at the time of surgery and reversing it when started after development of dry eye. Our results support the potential utility of CFTR\u2010targeted activators as a novel prosecretory treatment for dry eye.\u2014Flores, A. M., Casey, S. D., Felix, C. M., Phuan, P. W., Verkman, A. S., Levin, M. H. Small\u2010molecule CFTR activators increase tear secretion and prevent experimental dry eye disease.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    30, 1789\u20131797 (2016).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201500180","type":"journal-article","created":{"date-parts":[[2016,2,3]],"date-time":"2016-02-03T23:03:23Z","timestamp":1454540603000},"page":"1789-1797","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Small\u2010molecule CFTR activators increase tear secretion and prevent experimental dry eye disease"],"prefix":"10.1096","volume":"30","author":[{"given":"Alyssa M.","family":"Mores","sequence":"first","affiliation":[{"name":"Department of Medicine University of California, San Francisco San Francisco California USA"},{"name":"Department of Physiology University of California, San Francisco San Francisco California USA"},{"name":"Department of Ophthalmology University of California, San Francisco San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Casey","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California, San Francisco San Francisco California USA"},{"name":"Department of Physiology University of California, San Francisco San Francisco California USA"},{"name":"Department of Ophthalmology University of California, San Francisco San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian M.","family":"Felix","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California, San Francisco San Francisco California USA"},{"name":"Department of Physiology University of California, San Francisco San Francisco California USA"},{"name":"Department of Ophthalmology University of California, San Francisco San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puay W.","family":"Phuan","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California, San Francisco San Francisco California USA"},{"name":"Department of Physiology University of California, San Francisco San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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