{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T08:36:15Z","timestamp":1774773375845,"version":"3.50.1"},"reference-count":67,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2018,7,18]],"date-time":"2018-07-18T00:00:00Z","timestamp":1531872000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000310","name":"RP Fighting Blindness","doi-asserted-by":"publisher","award":["GR590"],"award-info":[{"award-number":["GR590"]}],"id":[{"id":"10.13039\/501100000310","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010757","name":"National Centre for the Replacement Refinement and Reduction of Animals in Research","doi-asserted-by":"publisher","award":["NC\/L001152\/1"],"award-info":[{"award-number":["NC\/L001152\/1"]}],"id":[{"id":"10.13039\/501100010757","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011718","name":"Macular Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011718","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Gift of Sight Appeal"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    The retinal pigment epithelium (RPE) plays a key role in the pathogenesis of several blinding retinopathies. Alterations to RPE structure and function are reported in Age-related Macular Degeneration, Stargardt and Best disease as well as pattern dystrophies. However, the precise role of RPE cells in disease aetiology remains incompletely understood. Many studies into RPE pathobiology have utilised animal models, which only recapitulate limited disease features. Some studies are also difficult to carry out in animals as the ocular space remains largely inaccessible to powerful microscopes. In contrast,\n                    <ns4:italic>in-vitro<\/ns4:italic>\n                    models provide an attractive alternative to investigating pathogenic RPE changes associated with age and disease. In this article we describe the step-by-step approach required to establish an experimentally versatile\n                    <ns4:italic>in-vitro<\/ns4:italic>\n                    culture model of the outer retina incorporating the RPE monolayer and supportive Bruch\u2019s membrane (BrM). We show that confluent monolayers of the spontaneously arisen human ARPE-19 cell-line cultured under optimal conditions reproduce key features of native RPE. These models can be used to study dynamic, intracellular and extracellular pathogenic changes using the latest developments in microscopy and imaging technology. We also discuss how RPE cells from human foetal and stem-cell derived sources can be incorporated alongside sophisticated BrM substitutes to replicate the aged\/diseased outer retina in a dish. The work presented here will enable users to rapidly establish a realistic\n                    <ns4:italic>in-vitro<\/ns4:italic>\n                    model of the outer retina that is amenable to a high degree of experimental manipulation which will also serve as an attractive alternative to using animals. This\n                    <ns4:italic>in-vitro<\/ns4:italic>\n                    model therefore has the benefit of achieving the 3Rs objective of reducing and replacing the use of animals in research. As well as recapitulating salient structural and physiological features of native RPE, other advantages of this model include its simplicity, rapid set-up time and unlimited scope for detailed single-cell resolution and matrix studies.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.15409.1","type":"journal-article","created":{"date-parts":[[2018,7,18]],"date-time":"2018-07-18T11:30:04Z","timestamp":1531913404000},"page":"1107","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["A convenient protocol for establishing a human cell culture model of the outer retina."],"prefix":"10.12688","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2513-3144","authenticated-orcid":false,"given":"Savannah A.","family":"Lynn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eloise","family":"Keeling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer M.","family":"Dewing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Johnston","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton","family":"Page","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela J.","family":"Cree","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5169-0561","authenticated-orcid":false,"given":"David A.","family":"Tumbarello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracey A.","family":"Newman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Lotery","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1027-6938","authenticated-orcid":false,"given":"J. Arjuna","family":"Ratnayaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2018,7,18]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"15-36","DOI":"10.1007\/978-1-4614-0653-2_2","article-title":"Age-related macular degeneration.","volume":"724","author":"S Khandhadia","year":"2012","journal-title":"Adv Exp Med Biol."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"295-317","DOI":"10.1016\/j.mam.2012.04.005","article-title":"Understanding age-related macular degeneration (AMD): relationships between the photoreceptor\/retinal pigment epithelium\/Bruch's membrane\/choriocapillaris complex.","volume":"33","author":"I Bhutto","year":"2012","journal-title":"Mol Aspects Med."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"413-24","DOI":"10.2147\/OPTH.S2151","article-title":"Age and disease-related structural changes in the retinal pigment 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Chau, Research Centre\u00a0inTopical Drug Delivery\u00a0and\u00a0Toxicology, Department of Pharmacy, Pharmacology and Postgraduate Medicine, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK, 14 Aug 2018, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/7-1107\/v1#referee-response-36346","order":0,"name":"referee-response-36346","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.16791.r37636, Ian J. Jackson, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK, 13 Sep 2018, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/7-1107\/v1#referee-response-37636","order":1,"name":"referee-response-37636","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was funded by awards to JAR from the National Centre for the Replacement, Refinement & Reduction of Animals in Research [NC\/L001152\/1], the Macular Society, RP Fighting Blindness [GR590] and the Gift of Sight Appeal.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Data associated with the article are available under the terms of the Creative Commons Zero \"No rights reserved\" data waiver (CC0 1.0 Public domain dedication).","order":0,"name":"copyright-info","label":"Copyright"}]}}