{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:18:28Z","timestamp":1790882308388,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"vor","delay-in-days":304,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["PA2018001057"],"award-info":[{"award-number":["PA2018001057"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>\n                    Age\u2010related macular degeneration (AMD) is a multifactor disease, which is primarily characterized by retinal pigment epithelium (RPE) cell loss. Since the retina is the most metabolically active tissue, RPE cells are exposed to consistent oxidative environment. So, oxidation\u2010induced RPE cell death has long been considered a contributor to the onset of AMD. Here, we applied a retinal degeneration (RD) rat model induced by blue light\u2010emitting diode (LED) and a cell model constructed by H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    stimulus to mimic the prooxidant environment of the retina. We detected that the expression of miR\u201027a was upregulated and the expression of FOXO1 was downregulated in both models. So, we furtherly investigated the role of miR\u201027a\u2010FOXO1 axis in RPE in protesting against oxidants. Lentivirus\u2010mediated RNA was injected intravitreally into rats to modulate the miR\u201027a\u2010FOXO1 axis. Retinal function and histopathological changes were evaluated by electroretinography (ERG) analysis and hematoxylin and eosin (H&amp;E) staining, respectively. Massive photoreceptor and RPE cell death were examined by terminal deoxynucleotidyl transferase\u2010mediated dUTP nick end labeling (TUNEL). The damage to the retina was aggravated in the FOXO1 gene\u2010knockdown and miR\u201027a\u2010overexpression groups after exposure to LED but was alleviated in the FOXO1 gene\u2010overexpression or miR\u201027a\u2010knockdown groups. Dual luciferase assay was used to detect the binding site of miR\u201027a and FOXO1. Upregulated miR\u201027a inhibited the expression of FOXO1 by directly binding to the FOXO1 mRNA 3\u2009\n                    <jats:sup>\u2032<\/jats:sup>\n                    UTR and decreased the autophagy activity of ARPE\u201019 cells, resulting in the accumulation of reactive oxygen species (ROS) and decrease of cell viability. The results suggest that miR\u201027a is a negative regulator of FOXO1. Also, our data emphasize the prominent role of miR\u201027a\/FOXO1 axis in modulating ROS accumulation and cell death in RPE cell model under oxidative stress and influencing the retinal function in the LED\u2010induced RD rat model.\n                  <\/jats:p>","DOI":"10.1155\/2021\/6666506","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T19:05:08Z","timestamp":1635793508000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["MicroRNA\u201027a Promotes Oxidative\u2010Induced RPE Cell Death through Targeting FOXO1"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5381-4265","authenticated-orcid":false,"given":"Chengda","family":"Ren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weinan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingquan","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2880-302X","authenticated-orcid":false,"given":"Wenting","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huizi","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghui","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijiang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5494-9949","authenticated-orcid":false,"given":"Xiuwei","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4899-0467","authenticated-orcid":false,"given":"Jing","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-008-0418-z"},{"key":"e_1_2_10_2_2","first-page":"844","article-title":"Global data on visual impairment in the year 2002","volume":"82","author":"Resnikoff S.","year":"2004","journal-title":"Bulletin of the World Health Organization"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11262-1"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.14-14827"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2012.03.009"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2017.03.002"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2020.108391"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1149460"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.01.008"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/bcr2484"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1159\/000467941"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2017.10.040"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/es4055516"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-08-0531"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12427"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06-0140"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2017.11.030"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.4266"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S176349"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-015-3258-x"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep05223"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1307294"},{"key":"e_1_2_10_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-009-9177-z"},{"key":"e_1_2_10_24_2","first-page":"932","article-title":"The protective effect of PEP-1-CAT fusion protein on hydrogen peroxide-induced oxidative stress injury in human umbilical vein endothelial cells","volume":"34","author":"Yao L. 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