{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T23:29:10Z","timestamp":1778282950375,"version":"3.51.4"},"reference-count":35,"publisher":"SLACK, Inc.","issue":"S1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ophthalmic Surg Lasers Imaging Retina"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND AND OBJECTIVE:<\/jats:title>\n            <jats:p>To investigate the effects of antiangiogenic drugs on the transcription profile of acetylation genes in immortalized human retinal pigment epithelium cells (ARPE-19) in vitro.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>MATERIALS AND METHODS:<\/jats:title>\n            <jats:p>\n              This in vitro study evaluated the effect of antiangiogenic drugs on the expression of histone acetylation genes on immortalized ARPE-19 cell cultures. ARPE-19 cells were cultured, plated, and treated for 24 hours with aflibercept (Eylea; Regeneron, Tarrytown, NY), ranibizumab (Lucentis; Genentech, South San Francisco, CA), or bevacizumab (Avastin; Genentech, South San Francisco, CA) at one (1\u00d7) or two times (2\u00d7) the concentrations of the clinical intravitreal dose. Untreated cells were used as controls. RNA was isolated, and real-time quantitative reverse transcription polymerase chain reaction analysis was performed on individual samples to quantify expression levels of genes associated with epigenetic acetylation pathways: histone acetyltransferase 1 (\n              <jats:italic>HAT1<\/jats:italic>\n              ) and histone deacetylases 1, 6, and 11 (\n              <jats:italic>HDAC1<\/jats:italic>\n              ,\n              <jats:italic>HDAC6<\/jats:italic>\n              , and\n              <jats:italic>HDAC11<\/jats:italic>\n              ). Differences in cycle thresholds (\u0394\u0394Cts) were obtained, and folds were calculated using the formula 2\n              <jats:sup>^\u0394\u0394Ct<\/jats:sup>\n              . Main outcome measures were expression levels of candidate genes in treated versus untreated samples.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Compared with untreated cells, 1\u00d7 ranibizumab-treated cells expressed higher levels of\n              <jats:italic>HDAC6<\/jats:italic>\n              , and 2\u00d7 ranibizumab-treated cells expressed higher\n              <jats:italic>HDAC11<\/jats:italic>\n              levels. Bevacizumab-treated (1\u00d7) cells had significant change in\n              <jats:italic>HDAC1<\/jats:italic>\n              ,\n              <jats:italic>HDAC6<\/jats:italic>\n              , and\n              <jats:italic>HDAC11<\/jats:italic>\n              . In cultures treated with 2\u00d7 bevacizumab, only\n              <jats:italic>HDAC11<\/jats:italic>\n              expression levels were significantly affected compared with controls. Aflibercept-treated (1\u00d7) cells had changes in expression of\n              <jats:italic>HDAC1<\/jats:italic>\n              ,\n              <jats:italic>HDAC6<\/jats:italic>\n              , and\n              <jats:italic>HDAC11<\/jats:italic>\n              . At 2\u00d7 concentration, only\n              <jats:italic>HDAC11<\/jats:italic>\n              was significantly changed.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION:<\/jats:title>\n            <jats:p>Our results show that antiangiogenic drugs can affect the transcription profile of genes regulating the histone acetylation status in ARPE-19 cells in vitro. This finding may have an implication in differential patient response to anti-vascular endothelial growth factor therapy by means of possible interactions between treatment and patient's epigenomic profile.<\/jats:p>\n            <jats:p>\n              <jats:bold>\n                [\n                <jats:italic>Ophthalmic Surg Lasers Imaging Retina<\/jats:italic>\n                . 2018;49:S29\u2013S33.]\n              <\/jats:bold>\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.3928\/23258160-20180814-05","type":"journal-article","created":{"date-parts":[[2018,10,18]],"date-time":"2018-10-18T17:32:16Z","timestamp":1539883936000},"source":"Crossref","is-referenced-by-count":3,"title":["Effects of Antiangiogenic Drugs on Expression Patterns of Epigenetic Pathway Genes"],"prefix":"10.3928","volume":"49","author":[{"given":"Mohamed A.","family":"Hamid","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed Tarek","family":"Moustafa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"C\u00e0ceres-del-Carpio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baruch D.","family":"Kuppermann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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