{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T18:48:41Z","timestamp":1780598921724,"version":"3.54.1"},"reference-count":53,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,11,9]],"date-time":"2020-11-09T00:00:00Z","timestamp":1604880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011718","name":"Macular Society","doi-asserted-by":"publisher","award":["PhD Studentship"],"award-info":[{"award-number":["PhD Studentship"]}],"id":[{"id":"10.13039\/100011718","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Gift of Sight Appeal","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The retinal pigment epithelium (RPE) is located between the neuroretina and the choroid, and plays a critical role in vision. RPE cells internalise outer segments (OS) from overlying photoreceptors in the daily photoreceptor renewal. Changes to RPE structure are linked with age and retinopathy, which has been described in the past by conventional 2D electron microscopy. We used serial block face scanning electron microscopy (SBF-SEM) to reconstruct RPE cells from the central mouse retina. Three-dimensional-reconstructed OS revealed the RPE to support large numbers of photoreceptors (90\u2013216 per RPE cell). Larger bi-nucleate RPE maintained more photoreceptors, although their cytoplasmic volume was comparable to smaller mono-nucleate RPE supporting fewer photoreceptors. Scrutiny of RPE microvilli and interdigitating OS revealed the angle and surface area of contact between RPE and photoreceptors. Bi-nucleate RPE contained more mitochondria compared to mono-nucleate RPE. Furthermore, bi-nucleate cells contained larger sub-RPE spaces, supporting a likely association with disease. Use of perfusion-fixed tissues ensured the highest possible standard of preservation, providing novel insights into the 3D RPE architecture and changes linked with retinopathy. This study serves as a benchmark for comparing retinal tissues from donor eyes with age-related macular degeneration (AMD) and other retinopathies.<\/jats:p>","DOI":"10.3390\/ijms21218408","type":"journal-article","created":{"date-parts":[[2020,11,9]],"date-time":"2020-11-09T19:08:29Z","timestamp":1604948909000},"page":"8408","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["3D-Reconstructed Retinal Pigment Epithelial Cells Provide Insights into the Anatomy of the Outer Retina"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0399-359X","authenticated-orcid":false,"given":"Eloise","family":"Keeling","sequence":"first","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP806, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Chatelet","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Unit, University of Southampton, MP12, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1782-4167","authenticated-orcid":false,"given":"Nicole Y. T.","family":"Tan","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP806, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farihah","family":"Khan","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP806, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhys","family":"Richards","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP806, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibana","family":"Thisainathan","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP806, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Goggin","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Unit, University of Southampton, MP12, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Page","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Unit, University of Southampton, MP12, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5169-0561","authenticated-orcid":false,"given":"David A.","family":"Tumbarello","sequence":"additional","affiliation":[{"name":"Biological Sciences, Faculty of Environmental and Life Sciences, Life Sciences Building 85, University of Southampton, Highfield Campus, Southampton SO17 1BJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5541-4305","authenticated-orcid":false,"given":"Andrew J.","family":"Lotery","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP806, Tremona Road, Southampton SO16 6YD, UK"},{"name":"Eye Unit, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1027-6938","authenticated-orcid":false,"given":"J. Arjuna","family":"Ratnayaka","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP806, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1001\/archopht.1968.00980050216012","article-title":"The retinal pigment epithelium: III. Growth and development","volume":"80","author":"Friedman","year":"1968","journal-title":"Arch. Ophthalmol. (Chic.)"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Marmor, M.F., and Wolfensberger, T. (1998). The retinal pigment epithelium. 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