{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:34:41Z","timestamp":1788186881205,"version":"build-2803163510"},"reference-count":70,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T00:00:00Z","timestamp":1535587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002089","name":"Fight for Sight","doi-asserted-by":"publisher","award":["1712\/13"],"award-info":[{"award-number":["1712\/13"]}],"id":[{"id":"10.13039\/100002089","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002089","name":"Fight for Sight","doi-asserted-by":"publisher","award":["1361\/1362"],"award-info":[{"award-number":["1361\/1362"]}],"id":[{"id":"10.13039\/100002089","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000317","name":"Action Medical Research","doi-asserted-by":"publisher","award":["GN2299"],"award-info":[{"award-number":["GN2299"]}],"id":[{"id":"10.13039\/501100000317","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2018,11]]},"abstract":"Abstract<\/jats:title>\n \n The transepithelial potential difference (\n TEP<\/jats:styled-content>\n ) across the retinal pigment epithelial (\n RPE<\/jats:styled-content>\n ) is dependent on ionic pumps and tight junction \u201cseals\u201d between epithelial cells.\n RPE<\/jats:styled-content>\n cells release neurotrophic growth factors such as pigment epithelial derived factor (\n PEDF<\/jats:styled-content>\n ), which is reduced in age\u2010related macular degeneration (\n AMD<\/jats:styled-content>\n ). The mechanisms that control the secretion of\n PEDF<\/jats:styled-content>\n from\n RPE<\/jats:styled-content>\n cells are not well understood. Using the\n CCL<\/jats:styled-content>\n 2\/\n CX<\/jats:styled-content>\n 3\n CR<\/jats:styled-content>\n 1 double knockout mouse model (\n DKO<\/jats:styled-content>\n ), which demonstrates\n RPE<\/jats:styled-content>\n damage and retinal degeneration, we uncovered an interaction between\n PEDF<\/jats:styled-content>\n and the\n TEP<\/jats:styled-content>\n which is likely to play an important role in retinal ageing and in the pathogenesis of\n AMD<\/jats:styled-content>\n . We found that: (a) the expression of\n ATP<\/jats:styled-content>\n 1B1 (the Na\n +<\/jats:sup>\n \/K\n +<\/jats:sup>\n \u2010\n ATP<\/jats:styled-content>\n ase \u03b21 subunit) was reduced significantly in\n RPE<\/jats:styled-content>\n from aged mice, in patients with\n CNV<\/jats:styled-content>\n (Choroidal Neovascularization) and in\n DKO<\/jats:styled-content>\n mice; (b) the expression of\n PEDF<\/jats:styled-content>\n also was decreased in aged persons and in\n DKO<\/jats:styled-content>\n mice; (c) the\n TEP<\/jats:styled-content>\n across\n RPE<\/jats:styled-content>\n was reduced markedly in\n RPE<\/jats:styled-content>\n cells from\n DKO<\/jats:styled-content>\n mice and (d) an applied electric field (\n EF<\/jats:styled-content>\n ) of 50\u2010100\u00a0mV\/mm, used to mimic the natural\n TEP<\/jats:styled-content>\n , increased the expression and secretion of\n PEDF<\/jats:styled-content>\n in primary\n RPE<\/jats:styled-content>\n cells. In conclusion, the\n TEP<\/jats:styled-content>\n across the\n RPE<\/jats:styled-content>\n depends on the expression of\n ATP<\/jats:styled-content>\n 1B1 and this regulates the secretion of\n PEDF<\/jats:styled-content>\n by\n RPE<\/jats:styled-content>\n cells and so may regulate the onset of retinal disease. Increasing the expression of\n PEDF<\/jats:styled-content>\n using an applied\n EF<\/jats:styled-content>\n to replenish a disease or age\u2010reduced\n TEP<\/jats:styled-content>\n may offer a new way of preventing or reversing retinal dysfunction.\n <\/jats:p>","DOI":"10.1111\/jcmm.13829","type":"journal-article","created":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T10:59:32Z","timestamp":1535626772000},"page":"5552-5564","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Polarized retinal pigment epithelium generates electrical signals that diminish with age and regulate retinal pathology"],"prefix":"10.1111","volume":"22","author":[{"given":"Lin","family":"Cao","sequence":"first","affiliation":[{"name":"School of Medicine Medical Sciences and Nutrition Institute of Medical Sciences University of Aberdeen Aberdeen UK"},{"name":"Yizhou International Proton Medical Centre and Cancer Hospital He Bei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Frist Hospital Affiliated to the Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3827-8924","authenticated-orcid":false,"given":"Jin","family":"Pu","sequence":"additional","affiliation":[{"name":"School of Medicine Medical Sciences and Nutrition Institute of Medical Sciences University of Aberdeen Aberdeen UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian","family":"Milne","sequence":"additional","affiliation":[{"name":"School of Medicine Medical Sciences and Nutrition Institute of Medical Sciences University of Aberdeen Aberdeen UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Chen","sequence":"additional","affiliation":[{"name":"Wellcome\u2010Wolfson Institute for Experimental Medicine Queen's University Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heping","family":"Xu","sequence":"additional","affiliation":[{"name":"Wellcome\u2010Wolfson Institute for Experimental Medicine Queen's University Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Shipley","sequence":"additional","affiliation":[{"name":"Biological Research & Development University of New England Biddeford Maine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John V","family":"Forrester","sequence":"additional","affiliation":[{"name":"School of Medicine Medical Sciences and Nutrition Institute of Medical Sciences University of Aberdeen Aberdeen UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin D","family":"McCaig","sequence":"additional","affiliation":[{"name":"School of Medicine Medical Sciences and Nutrition Institute of Medical Sciences University of Aberdeen Aberdeen UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noemi","family":"Lois","sequence":"additional","affiliation":[{"name":"Wellcome\u2010Wolfson Institute for Experimental Medicine Queen's University Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,30]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"1691","article-title":"Cell loss in the aging retina. 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