{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T05:18:15Z","timestamp":1791955095362,"version":"4.3.4"},"reference-count":72,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T00:00:00Z","timestamp":1673827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["#MR\/S035826\/1"],"award-info":[{"award-number":["#MR\/S035826\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Biotechnology and Biosciences Research Council","award":["#BB\/T004460\/1"],"award-info":[{"award-number":["#BB\/T004460\/1"]}]},{"name":"Wellcome Trust Human Developmental Biology Resource","award":["#MR\/R006237\/1"],"award-info":[{"award-number":["#MR\/R006237\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Age-related macular degeneration (AMD) is the most prevalent cause of blindness in the developed world. Vision loss in the advanced stages of the disease is caused by atrophy of retinal photoreceptors, overlying retinal pigment epithelium (RPE) and choroidal endothelial cells. The molecular events that underline the development of these cell types from in utero to adult as well as the progression to intermediate and advanced stages AMD are not yet fully understood. We performed single-cell RNA-sequencing (RNA-Seq) of human fetal and adult RPE\u2013choroidal tissues, profiling in detail all the cell types and elucidating cell type-specific proliferation, differentiation and immunomodulation events that occur up to midgestation. Our data demonstrate that progression from the fetal to adult state is characterized by an increase in expression of genes involved in the oxidative stress response and detoxification from heavy metals, suggesting a better defence against oxidative stress in the adult RPE\u2013choroid tissue. Single-cell comparative transcriptional analysis between a patient with intermediate AMD and an unaffected subject revealed a reduction in the number of RPE cells and melanocytes in the macular region of the AMD patient. Together these findings may suggest a macular loss of RPE cells and melanocytes in the AMD patients, but given the complex processing of tissues required for single-cell RNA-Seq that is prone to technical artefacts, these findings need to be validated by additional techniques in a larger number of AMD patients and controls.<\/jats:p>","DOI":"10.1093\/hmg\/ddad007","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T12:48:22Z","timestamp":1673873302000},"page":"1698-1710","source":"Crossref","is-referenced-by-count":43,"title":["Single-cell RNA sequencing reveals transcriptional changes of human choroidal and retinal pigment epithelium cells during fetal development, in healthy adult and intermediate age-related macular degeneration"],"prefix":"10.1093","volume":"32","author":[{"given":"Joseph","family":"Collin","sequence":"first","affiliation":[{"name":"Biosciences Institute , Faculty of Medical Sciences, , Newcastle, NE1 3BZ , UK"},{"name":"Newcastle University , Faculty of Medical Sciences, , Newcastle, NE1 3BZ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan S R","family":"Hasoon","sequence":"additional","affiliation":[{"name":"Biosciences Institute , Faculty of Medical Sciences, , Newcastle, NE1 3BZ , UK"},{"name":"Newcastle University , Faculty of Medical Sciences, , Newcastle, NE1 3BZ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darin","family":"Zerti","sequence":"additional","affiliation":[{"name":"Biosciences Institute , Faculty of Medical Sciences, , Newcastle, NE1 3BZ , UK"},{"name":"Newcastle University , Faculty of Medical Sciences, , Newcastle, NE1 3BZ , UK"},{"name":"Microscopy Centre and Department of Applied Clinical Sciences and Biotechnology, University of L\u2019Aquila , L'aquila 67100 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Hammadi","sequence":"additional","affiliation":[{"name":"Biosciences Institute , Faculty 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Res."},{"key":"2023050516332690000_ref37","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.bbrc.2009.03.034","article-title":"Interleukin-6 induces proinflammatory signaling in Schwann cells: a high-throughput analysis","volume":"382","author":"Lee","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2023050516332690000_ref38","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1111\/pcmr.12972","article-title":"The role of melanocytes in the human choroidal microenvironment and inflammation: insights from the transcriptome","volume":"34","author":"Cioanca","year":"2021","journal-title":"Pigment. Cell Melanoma Res."},{"key":"2023050516332690000_ref39","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/aja.1001320113","article-title":"The development of pigment cells in the eyes of rhesus monkeys","volume":"132","author":"Hu","year":"1971","journal-title":"Am. J. Anat."},{"key":"2023050516332690000_ref40","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/0012-1606(73)90220-0","article-title":"Pigment cell development in rhesus monkey eyes: an electron microscopic and histochemical study","volume":"32","author":"Endo","year":"1973","journal-title":"Dev. Biol."},{"key":"2023050516332690000_ref41","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1167\/iovs.61.10.33","article-title":"Melanoblasts populate the mouse choroid earlier in development than previously described","volume":"61","author":"McMenamin","year":"2020","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2023050516332690000_ref42","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.molmed.2006.07.008","article-title":"MITF: master regulator of melanocyte development and melanoma oncogene","volume":"12","author":"Levy","year":"2006","journal-title":"Trends Mol. Med."},{"key":"2023050516332690000_ref43","first-page":"68","article-title":"Pericyte form and distribution in rat retinal and uveal capillaries","volume":"26","author":"Tilton","year":"1985","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2023050516332690000_ref44","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1152\/physrev.00041.2003","article-title":"Molecular regulation of vascular smooth muscle cell differentiation in development and disease","volume":"84","author":"Owens","year":"2004","journal-title":"Physiol. Rev."},{"key":"2023050516332690000_ref45","doi-asserted-by":"crossref","first-page":"8361","DOI":"10.1074\/jbc.M111.286203","article-title":"A novel RhoA\/ROCK-CPI-17-MEF2C signaling pathway regulates vascular smooth muscle cell gene expression","volume":"287","author":"Pagiatakis","year":"2012","journal-title":"J. Biol. 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