{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T20:16:05Z","timestamp":1777580165776,"version":"3.51.4"},"reference-count":26,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Ophthalmology"],"published-print":{"date-parts":[[2016,9]]},"abstract":"\n Purpose<\/jats:title>\n The neovascular or wet form of age-related macular degeneration is characterized by the growth of abnormal blood vessels in the retina stimulated by vascular endothelial growth factors (VEGF). In the last decade, several anti-VEGF drugs have been developed for treating neovascular diseases of the eyes. This study was conducted to compare the effects of 2 anti-VEGF-A drugs, ranibizumab and aflibercept, on the expression and secretion of VEGF family members in retinal pigment epithelial cells (RPE) in vitro.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n ARPE-19 cells were exposed for 24 hours to ranibizumab or aflibercept at clinical dose concentration. Cell viability and expression and secretion of VEGF-A, VEGF-B, VEGF-C, and placental growth factor (PlGF) were evaluated respectively by real-time polymerase chain reaction and enzyme-linked immunosorbent assay.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Ranibizumab and aflibercept did not affect ARPE-19 cell viability after 24 hours of treatment. Ranibizumab increased expression of VEGF-A and PlGF. On the contrary, expression and secretion of VEGF-C was decreased by ranibizumab. PlGF secretion was not affected by ranibizumab. Aflibercept strongly increased VEGF-A and PlGF expression but reduced their detection on the culture media, and decreased expression and secretion of VEGF-C. No effect on expression and secretion of VEGF-B was observed after exposure to these drugs.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Ranibizumab and aflibercept exert similar effects on VEGF expression and secretion, leading to establishing an antiangiogenic environment. Increased VEGF-A expression observed in RPE cells treated with these drugs suggests a compensatory response of the cells to the lack of VEGF-A.<\/jats:p>\n <\/jats:sec>","DOI":"10.5301\/ejo.5000786","type":"journal-article","created":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T04:10:46Z","timestamp":1460693446000},"page":"425-430","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Response to Anti-VEGF-A Treatment of Retinal Pigment Epithelial Cells\n In Vitro<\/i>"],"prefix":"10.1177","volume":"26","author":[{"given":"Alessandra","family":"Puddu","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Medical Specialties, Genova - Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Sanguineti","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialties, Genova - Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo Enrico","family":"Traverso","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Ophthalmology and Genetics, Genova - Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgio L.","family":"Viviani","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Medical Specialties, Genova - Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Nicol\u00f2","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Ophthalmology and Genetics, Genova - Italy"},{"name":"Fondazione per la Macula onlus, Genova - Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2016,12,4]]},"reference":[{"key":"bibr1-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1001\/jama.291.15.1900"},{"key":"bibr2-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2009.06.045"},{"key":"bibr3-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.259re1"},{"key":"bibr4-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1038\/35025220"},{"key":"bibr5-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1097\/01.iae.0000242842.14624.e7"},{"key":"bibr6-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1177\/2040622312446007"},{"key":"bibr7-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2710.2007.00800.x"},{"key":"bibr8-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.172398299"},{"key":"bibr9-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1038\/87904"},{"key":"bibr10-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1042\/CS20040370"},{"key":"bibr11-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2006.101543"},{"key":"bibr12-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2006.091215"},{"key":"bibr13-ejo.5000786","first-page":"2509","volume":"18","author":"Puddu A","year":"2012","journal-title":"Mol Vis"},{"key":"bibr14-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-014-2719-y"},{"key":"bibr15-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-009-1136-0"},{"key":"bibr16-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0905010106"},{"key":"bibr17-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"bibr18-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1124\/mol.106.027029"},{"key":"bibr19-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1097\/IAE.0b013e31827b646d"},{"key":"bibr20-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2014-305302"},{"key":"bibr21-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2013-303130"},{"key":"bibr22-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-4144"},{"key":"bibr23-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.46.30336"},{"key":"bibr24-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2004.07.004"},{"key":"bibr25-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.01.017"},{"key":"bibr26-ejo.5000786","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0813061106"}],"container-title":["European Journal of Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.5301\/ejo.5000786","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.5301\/ejo.5000786","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.5301\/ejo.5000786","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T19:40:18Z","timestamp":1777405218000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.5301\/ejo.5000786"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9]]},"references-count":26,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2016,9]]}},"alternative-id":["10.5301\/ejo.5000786"],"URL":"https:\/\/doi.org\/10.5301\/ejo.5000786","relation":{},"ISSN":["1120-6721","1724-6016"],"issn-type":[{"value":"1120-6721","type":"print"},{"value":"1724-6016","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9]]}}}