{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T22:46:57Z","timestamp":1777934817306,"version":"3.51.4"},"reference-count":81,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"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"],"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>This study aimed to evaluate the neuroprotective effects of cutamesine (SA4503), a potent sigma-1-receptor agonist (S1R-agonist), in rat models of retinal degeneration induced by elevated intraocular pressure (IOP) using the Detection of Apoptosing Retinal Cells (DARC) technology. A secondary aim was to test its effect in a rat retinal oxidative stress model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Ocular hypertension (OHT) model was induced in Dark Agouti rats via episcleral vein injection of hypertonic saline, while a retinal oxidative stress was induced in Sprague-Dawley rats by intravitreal rotenone injection. In the OHT model, cutamesine (10 nmol) and recombinant human nerve growth factor [rh-NGF (positive control); 0.09 nmol] were intravitreally administered. Their effects were evaluated using DARC technology and RNA-binding protein with multiple splicing (RBPMS) immunohistochemistry. In the oxidative stress model, cutamesine (10 and 300 nmol) was coadministered with rotenone, and neurofilament light chain (Nfl) gene expression was measured by RT-PCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      OHT induced a significant elevation of IOP over 3 weeks, peaked at day 1 (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001), and gradually decreased by day 21. Cutamesine significantly reduced the number of DARC spots (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05) and preserved retinal ganglion cells labeled with RBPMS (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.01), similar to rh-NGF (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.01). In the oxidative stress model, cutamesine preserved retinal Nfl expression levels in a dose-dependent manner.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Cutamesine demonstrated significant neuroprotective activity in rat models of OHT and oxidative stress using DARC and RBPMS labeling techniques. These findings provide further evidence that S1R-agonists possess substantial neuroprotective potential and may be beneficial for patients with OHT\/glaucoma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10807683251389754","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T15:00:31Z","timestamp":1761318031000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cutamesine (SA4503) Protects Retinal Ganglion Cells in an Ocular Hypertension Model of Glaucoma Determined Using Detection of Apoptosing Retinal Cells\u00a0Technology and RBPMS Cell Marker"],"prefix":"10.1177","author":[{"given":"Najam A.","family":"Sharif","sequence":"first","affiliation":[{"name":"Ophthalmology Innovation Center, Santen Inc., Emeryville, California, USA."},{"name":"Institute of Ophthalmology, University College London (UCL), London, United Kingdom."},{"name":"Imperial College of Science and Technology, St. Mary\u2019s Campus, London, United Kingdom."},{"name":"Eye-ACP Duke-National University of Singapore Medical School, Singapore, Singapore."},{"name":"Singapore Eye Research Institute (SERI), Singapore, Singapore."},{"name":"Department of Pharmacy Sciences, Creighton University, Omaha, Nebraska, USA."},{"name":"Department of Pharmacology and Neuroscience, University of North Texas Health Sciences Center, Fort Worth, Texas, USA."},{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas, USA."},{"name":"Global Research and Development, Nanoscope Therapeutics Inc., Dallas, Texas, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Ota","sequence":"additional","affiliation":[{"name":"Ophthalmology Innovation Center, Santen Pharmaceutical Co., Ltd., Nara, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takazumi","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Ophthalmology Innovation Center, Santen Pharmaceutical Co., Ltd., Nara, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaaki","family":"Sasaoka","sequence":"additional","affiliation":[{"name":"Ophthalmology Innovation Center, Santen Pharmaceutical Co., Ltd., Nara, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London (UCL), London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soyoung","family":"Choi","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London (UCL), London, United Kingdom."},{"name":"Novai Ltd., Reading, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vy","family":"Luong","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London (UCL), London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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