{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:30:32Z","timestamp":1790634632163,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T00:00:00Z","timestamp":1696550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health and Welfare, Republic of Korea","award":["HI16C1559"],"award-info":[{"award-number":["HI16C1559"]}]},{"name":"Ministry of Health and Welfare, Republic of Korea","award":["2021R1A2C201052311"],"award-info":[{"award-number":["2021R1A2C201052311"]}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["HI16C1559"],"award-info":[{"award-number":["HI16C1559"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["2021R1A2C201052311"],"award-info":[{"award-number":["2021R1A2C201052311"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Axonal degeneration resulting from optic nerve damage can lead to the progressive death of retinal ganglion cells (RGCs), culminating in irreversible vision loss. We contrasted two methods for inducing optic nerve damage: optic nerve compression (ONCo) and optic nerve crush (ONCr). These were assessed for their respective merits in simulating traumatic optic neuropathies and neurodegeneration. We also administered neural progenitor cells (NPCs) into the subtenon space to validate their potential in mitigating optic nerve damage. Our findings indicate that both ONCo and ONCr successfully induced optic nerve damage, as shown by increases in ischemia and expression of genes linked to neuronal regeneration. Post NPC injection, recovery in the expression of neuronal regeneration-related genes was more pronounced in the ONCo model than in the ONCr model, while inflammation-related gene expression saw a better recovery in ONCr. In addition, the proteomic analysis of R28 cells in hypoxic conditions identified Vps35 and Syntaxin12 genes. Vps35 preserved the mitochondrial function in ONCo, while Syntaxin12 appeared to restrain inflammation via the Wnt\/\u03b2-catenin signaling pathway in ONCr. NPCs managed to restore damaged RGCs by elevating neuroprotection factors and controlling inflammation through mitochondrial homeostasis and Wnt\/\u03b2-catenin signaling in hypoxia-injured R28 cells and in both animal models. Our results suggest that ischemic injury and crush injury cause optic nerve damage via different mechanisms, which can be effectively simulated using ONCo and ONCr, respectively. Moreover, cell-based therapies such as NPCs may offer promising avenues for treating various optic neuropathies, including ischemic and crush injuries.<\/jats:p>","DOI":"10.3390\/cells12192412","type":"journal-article","created":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T07:49:29Z","timestamp":1696578569000},"page":"2412","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Unveiling Neuroprotection and Regeneration Mechanisms in Optic Nerve Injury: Insight from Neural Progenitor Cell Therapy with Focus on Vps35 and Syntaxin12"],"prefix":"10.3390","volume":"12","author":[{"given":"Hyun-Ah","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Biomedical Science, CHA University, Pocheon-si 13488, Gyeonggi-Do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, CHA Medical Center, CHA University, Pocheon-si 13488, Gyeonggi-Do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hey Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"CHA Advanced Research Institute, CHA University, Pocheon-si 13488, Gyeonggi-Do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4676-1804","authenticated-orcid":false,"given":"Van-An","family":"Duong","sequence":"additional","affiliation":[{"name":"Gachon Institute of Pharmaceutical Sciences, Gachon College of Pharmacy, Gachon University, Incheon 21936, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5827-6956","authenticated-orcid":false,"given":"Hyun-Mun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, CHA University, Pocheon-si 13488, Gyeonggi-Do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Youn","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, CHA University, Pocheon-si 13488, Gyeonggi-Do, Republic of Korea"},{"name":"Department of Microbiology, School of Medicine, CHA University, Pocheon-si 13488, Gyeonggi-Do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8832-6587","authenticated-orcid":false,"given":"Hookeun","family":"Lee","sequence":"additional","affiliation":[{"name":"Gachon Institute of Pharmaceutical Sciences, Gachon College of Pharmacy, Gachon University, Incheon 21936, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0121-3000","authenticated-orcid":false,"given":"Helen","family":"Lew","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, CHA Medical Center, CHA University, Pocheon-si 13488, Gyeonggi-Do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1167\/iovs.15-17841","article-title":"Apoptotic Retinal Ganglion Cell Death After Optic Nerve Transection or Crush in Mice: Delayed RGC Loss With BDNF or a Caspase 3 Inhibitor","volume":"57","year":"2016","journal-title":"Invest. 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