{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T15:53:04Z","timestamp":1777909984978,"version":"3.51.4"},"reference-count":39,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"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":["Journal of Ocular Pharmacology and Therapeutics"],"published-print":{"date-parts":[[2022,9,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>Determine whether NCX 470, a nitric oxide (NO)-donating bimatoprost with clinically demonstrated intraocular pressure (IOP)-lowering effects, improves ocular hemodynamics and retinal physiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Endothelin-1 (ET-1)-induced ischemia\/reperfusion model in New Zealand white rabbits was used. ET-1 was injected next to the optic nerve twice\/week (Monday and Thursday) for 6 weeks. Starting on week 3, animals received NCX 470 (0.1% bid, 6 days\/week Monday\u2013Saturday) or vehicle until the end of ET-1 treatment. IOP, ophthalmic artery resistive index (OA-RI) and retina physiology (electroretinogram, ERG) were determined before dosing and at different times post-dosing. All measurements were taken on Mondays before the AM daily dosing (36\u2009h treatment-free). Finally, oxidative stress markers were determined in dissected retina and iris\/ciliary body of treated eyes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Injection of ET-1 progressively increased IOP (20.7\u2009\u00b1\u20090.6, 24.9\u2009\u00b1\u20091.2, and 27.0\u2009\u00b1\u20090.6\u2009mmHg at baseline, week 2 and 6, respectively) and OA-RI (0.30\u2009\u00b1\u20090.02, 0.39\u2009\u00b1\u20090.02, and 0.42\u2009\u00b1\u20090.03 at baseline, week 2 and 6, respectively) and reduced rods and\/or cones response as indicated by changes in ERG amplitudes under different stimulating conditions. NCX 470 re-established baseline IOP (21.8\u2009\u00b1\u20091.0\u2009mmHg), OA-RI (0.33\u2009\u00b1\u20090.02), and ERG amplitude by week 6 (mostly rod response,\n                      <jats:sup>0.01<\/jats:sup>\n                      Dark_A\n                      <jats:sub>Veh_6week<\/jats:sub>\n                      \u2009=\u200932.2\u2009\u00b1\u20093.0\u2009\u03bcV and\n                      <jats:sup>0.01<\/jats:sup>\n                      Dark_A\n                      <jats:sub>NCX470_6week<\/jats:sub>\n                      44.3\u2009\u00b1\u20094.5\u2009\u03bcV; mostly cone response,\n                      <jats:sup>3.0<\/jats:sup>\n                      Dark_A\n                      <jats:sub>Veh_6week<\/jats:sub>\n                      \u2009=\u200987.6\u2009\u00b1\u200910.1\u2009\u03bcV and\n                      <jats:sup>3.0<\/jats:sup>\n                      Dark_A\n                      <jats:sub>NCX470_6week<\/jats:sub>\n                      \u2009=\u2009122.8\u2009\u00b1\u200911.4\u2009\u03bcV; combined rod\/cone response,\n                      <jats:sup>3.0<\/jats:sup>\n                      Light_A\n                      <jats:sub>Veh_6week<\/jats:sub>\n                      \u2009=\u200949.8\u2009\u00b1\u20096.5\u2009\u03bcV and\n                      <jats:sup>3.0<\/jats:sup>\n                      Light_A\n                      <jats:sub>NCX470_6week<\/jats:sub>\n                      \u2009=\u200964.2\u2009\u00b1\u20096.8\u2009\u03bcV). NCX 470 also reversed ET-1-induced changes in glutathione and manganese superoxide dismutase (oxidative stress markers) in retina and iris\/ciliary body.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Repeated ocular topical dosing with NCX 470 reverses ET-1-induced changes in IOP, OA-RI, and ERG suggesting improved ocular hemodynamics and retinal physiology likely independently from its demonstrated IOP-lowering effect.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/jop.2022.0004","type":"journal-article","created":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T11:53:31Z","timestamp":1657022011000},"page":"496-504","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["NCX 470 Restores Ocular Hemodynamics and Retinal Cell Physiology After ET-1-Induced Ischemia\/Reperfusion Injury of Optic Nerve and Retina in Rabbits"],"prefix":"10.1177","volume":"38","author":[{"given":"Elena","family":"Bastia","sequence":"first","affiliation":[{"name":"Nicox Research Institute, Bresso, Milan, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Sgambellone","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology, University of Florence, Florence, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9016-8429","authenticated-orcid":false,"given":"Laura","family":"Lucarini","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology, University of Florence, Florence, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6182-6848","authenticated-orcid":false,"given":"Gustavo","family":"Provensi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology, University of Florence, Florence, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Brambilla","sequence":"additional","affiliation":[{"name":"Nicox Research Institute, Bresso, Milan, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinna","family":"Galli","sequence":"additional","affiliation":[{"name":"Nicox Research Institute, Bresso, Milan, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicoletta","family":"Almirante","sequence":"additional","affiliation":[{"name":"Nicox Research Institute, Bresso, Milan, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Impagnatiello","sequence":"additional","affiliation":[{"name":"Nicox Research Institute, Bresso, Milan, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2022,9,12]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-17190"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707434"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-0494"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.14-14515"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17-22168"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40123-017-0094-6"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6257(97)80008-2"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6257(02)00306-5"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41433-019-0633-6"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41433-018-0042-2"},{"key":"e_1_3_5_12_2","first-page":"224","article-title":"Oxygen and blood flow: players in the pathogenesis of glaucoma","volume":"14","author":"Mozaffarieh M.","year":"2008","unstructured":"Mozaffarieh M., , Grieshaber M.C., , and Flammer J. 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