{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:18:26Z","timestamp":1790936306295,"version":"4.1.0"},"reference-count":68,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,3,8]],"date-time":"2018-03-08T00:00:00Z","timestamp":1520467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670873"],"award-info":[{"award-number":["81670873"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Retinopathy of prematurity (<jats:styled-content style=\"fixed-case\">ROP<\/jats:styled-content>) is a retinopathy characterized by retinal neovascularization (<jats:styled-content style=\"fixed-case\">RNV<\/jats:styled-content>) occurring in preterm infants treated with high concentrations of oxygen and may lead to blindness in severe cases. Currently, anti\u2010<jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> therapy is a major treatment for <jats:styled-content style=\"fixed-case\">ROP<\/jats:styled-content>, but it is costly and may cause serious complications. The previous study has demonstrated that melatonin exerted neuroprotective effect against retinal ganglion cell death induced by hypoxia in neonatal rats. However, whether melatonin is anti\u2010angiogenic and neuroglial protective in the progression of <jats:styled-content style=\"fixed-case\">ROP<\/jats:styled-content> remains unknown. Thus, this study was to investigate the effect of melatonin on <jats:styled-content style=\"fixed-case\">RNV<\/jats:styled-content> and neuroglia in the retina of oxygen\u2010induced retinopathy (<jats:styled-content style=\"fixed-case\">OIR<\/jats:styled-content>) mice. The results showed a reduction in retinal vascular leakage in <jats:styled-content style=\"fixed-case\">OIR<\/jats:styled-content> mice after melatonin treatment. Besides, the size of retinal neovascular and avascular areas, the number of preretinal neovascular cell nuclei, and the number of proliferative vascular endothelial cells within the neovascular area were significantly decreased in mice treated with melatonin. After oxygen\u2010induced injury, the density of astrocytes was decreased, accompanied by morphologic and functional changes of astrocytes. Besides, retinal microglia were also activated. Meanwhile, the levels of inflammatory factors were elevated. However, these pathologic processes were all hindered by melatonin treatment. Furthermore, <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1\u2010<jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> pathway was activated in the retina of <jats:styled-content style=\"fixed-case\">OIR<\/jats:styled-content> mice, yet was suppressed in melatonin\u2010treated <jats:styled-content style=\"fixed-case\">OIR<\/jats:styled-content> mice retinas. In conclusion, melatonin prevented pathologic neovascularization, protected neuroglial cells, and exerts anti\u2010inflammation effect via inhibition of <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1\u2010<jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> pathway in <jats:styled-content style=\"fixed-case\">OIR<\/jats:styled-content> retinas, suggesting that melatonin could be a promising therapeutic agent for <jats:styled-content style=\"fixed-case\">ROP<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/jpi.12473","type":"journal-article","created":{"date-parts":[[2018,2,7]],"date-time":"2018-02-07T13:16:38Z","timestamp":1518009398000},"source":"Crossref","is-referenced-by-count":111,"title":["Melatonin attenuated retinal neovascularization and neuroglial dysfunction by inhibition of <scp>HIF<\/scp>\u20101\u03b1\u2010<scp>VEGF<\/scp> pathway in oxygen\u2010induced retinopathy mice"],"prefix":"10.1111","volume":"64","author":[{"given":"Yue","family":"Xu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010sen University  Guangzhou Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010sen University  Guangzhou Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaguang","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010sen University  Guangzhou Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyu","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010sen University  Guangzhou Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching\u2010Kit","family":"Tsui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010sen University  Guangzhou Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010sen University  Guangzhou Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010sen University  Guangzhou Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5753-5100","authenticated-orcid":false,"given":"Xiaoling","family":"Liang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010sen University  Guangzhou Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60178-6"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2016-308828"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2016.09.008"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2007.02.002"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.113.301331"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/apa.13586"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000431129"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10633-009-9201-x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-013-2366-8"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0603-669"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.13.1.9"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.3109\/08820538.2015.1114847"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpc.12860"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2014.08.011"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2011-301148"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-013-0993-5"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2009.00742.x"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0126750"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2005.08.020"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12383"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2012.01.003"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12227"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12263"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12413"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0154427"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12410"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12264"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12362"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12360"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12196"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2010.00816.x"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2010.00762.x"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12428"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12318"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2011.00913.x"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12008"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12016"},{"key":"e_1_2_7_39_1","first-page":"101","article-title":"Oxygen\u2010induced retinopathy in the mouse","volume":"35","author":"Smith LE","year":"1994","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-9315"},{"key":"e_1_2_7_41_1","first-page":"789","article-title":"Sensitive blood\u2010retinal barrier breakdown quantitation using Evans blue","volume":"42","author":"Xu Q","year":"2001","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05571"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200302047"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2007.00498.x"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22325"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1420"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12007"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12398"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12356"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12430"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2014.11.004"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2012.04.004"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2013.06.001"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-230284"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6758"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-11492"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1522"},{"key":"e_1_2_7_58_1","first-page":"467","article-title":"Microglia and macrophages are increased in response to ischemia\u2010induced retinopathy in the mouse retina","volume":"12","author":"Davies MH","year":"2006","journal-title":"Mol Vis"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1358"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.2002.00066.x"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aaa8695"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707302104"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000258979.92828.bc"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1187"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.113.089623"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4381-5"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12173"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2017.12.001"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18040763"}],"container-title":["Journal of Pineal Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjpi.12473","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jpi.12473","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T16:15:09Z","timestamp":1695572109000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jpi.12473"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,8]]},"references-count":68,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1111\/jpi.12473"],"URL":"https:\/\/doi.org\/10.1111\/jpi.12473","archive":["Portico"],"relation":{},"ISSN":["0742-3098","1600-079X"],"issn-type":[{"value":"0742-3098","type":"print"},{"value":"1600-079X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,8]]},"article-number":"e12473"}}