{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:00Z","timestamp":1787027820365,"version":"build-2736575974"},"reference-count":37,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["22390327"],"award-info":[{"award-number":["22390327"]}]},{"name":"JSPS KAKENHI","award":["24659770"],"award-info":[{"award-number":["24659770"]}]},{"name":"JSPS KAKENHI","award":["28-2"],"award-info":[{"award-number":["28-2"]}]},{"name":"JSPS KAKENHI","award":["2020B-5"],"award-info":[{"award-number":["2020B-5"]}]},{"DOI":"10.13039\/100007786","name":"National Center for Child Health and Development","doi-asserted-by":"publisher","award":["22390327"],"award-info":[{"award-number":["22390327"]}],"id":[{"id":"10.13039\/100007786","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007786","name":"National Center for Child Health and Development","doi-asserted-by":"publisher","award":["24659770"],"award-info":[{"award-number":["24659770"]}],"id":[{"id":"10.13039\/100007786","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007786","name":"National Center for Child Health and Development","doi-asserted-by":"publisher","award":["28-2"],"award-info":[{"award-number":["28-2"]}],"id":[{"id":"10.13039\/100007786","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007786","name":"National Center for Child Health and Development","doi-asserted-by":"publisher","award":["2020B-5"],"award-info":[{"award-number":["2020B-5"]}],"id":[{"id":"10.13039\/100007786","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Retinal ganglion cells (RGCs) are specialized projection neurons that constitute part of the retina, and the death of RGCs causes various eye diseases, but the mechanism of RGC death is still unclear. Here, we induced cell death in human induced pluripotent stem cell (hiPSC)-derived RGC-rich retinal tissues using hypoxia\u2013reoxygenation in vitro. Flow cytometry, immunochemistry, and Western blotting showed the apoptosis and necrosis of RGCs under hypoxia\u2013reoxygenation, and they were rescued by an apoptosis inhibitor but not by a necrosis inhibitor. This revealed that the cell death induced in our model was mainly due to apoptosis. To our knowledge, this is the first model to reproduce ischemia\u2013reperfusion in hiPSC-derived RGCs. Thus, the efficacy of apoptosis inhibitors and neuroprotective agents can be evaluated using this model, bringing us closer to clinical applications.<\/jats:p>","DOI":"10.3390\/cells13020130","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T03:21:41Z","timestamp":1704943301000},"page":"130","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Modeling of Retina and Optic Nerve Ischemia\u2013Reperfusion Injury through Hypoxia\u2013Reoxygenation in Human Induced Pluripotent Stem Cell-Derived Retinal Ganglion Cells"],"prefix":"10.3390","volume":"13","author":[{"given":"Tomoyo","family":"Yoshida","sequence":"first","affiliation":[{"name":"National Center for Child Health and Development, 2-10-1, O-kura, Setagaya-ku, Tokyo 1578535, Japan"},{"name":"Department of Pathological Cell Biology, Tokyo Medical and Dental University, 1-5-4, Yushima, Bunkyo-ku, Tokyo 1138510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Yokoi","sequence":"additional","affiliation":[{"name":"National Center for Child Health and Development, 2-10-1, O-kura, Setagaya-ku, Tokyo 1578535, Japan"},{"name":"Department of ophthalmology, Kyorin University, 6-20-2, Arakawa, Mitaka, Tokyo 1818611, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Tanaka","sequence":"additional","affiliation":[{"name":"National Center for Child Health and Development, 2-10-1, O-kura, Setagaya-ku, Tokyo 1578535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiko","family":"Matsuzaka","sequence":"additional","affiliation":[{"name":"National Center for Child Health and Development, 2-10-1, O-kura, Setagaya-ku, Tokyo 1578535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Saida","sequence":"additional","affiliation":[{"name":"National Center for Child Health and Development, 2-10-1, O-kura, Setagaya-ku, Tokyo 1578535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Nishina","sequence":"additional","affiliation":[{"name":"National Center for Child Health and Development, 2-10-1, O-kura, Setagaya-ku, Tokyo 1578535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Takada","sequence":"additional","affiliation":[{"name":"National Center for Child Health and Development, 2-10-1, O-kura, Setagaya-ku, Tokyo 1578535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8437-0791","authenticated-orcid":false,"given":"Shigeomi","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Pathological Cell Biology, Tokyo Medical and Dental University, 1-5-4, Yushima, Bunkyo-ku, Tokyo 1138510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyuki","family":"Azuma","sequence":"additional","affiliation":[{"name":"National Center for Child Health and Development, 2-10-1, O-kura, Setagaya-ku, Tokyo 1578535, Japan"},{"name":"Department of Developmental and Regenerative Biology, Tokyo Medical and Dental University, 1-5-4, Yushima, Bunkyo-ku, Tokyo 1138510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.preteyeres.2013.07.001","article-title":"Retinal ganglion cells: Energetics, compartmentation, axonal transport, cytoskeletons and vulnerability","volume":"36","author":"Yu","year":"2013","journal-title":"Prog. 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