{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:30:17Z","timestamp":1790634617669,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T00:00:00Z","timestamp":1669075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea Health Industry Development Institute (KHIDI)","award":["HI16C1559"],"award-info":[{"award-number":["HI16C1559"]}]},{"name":"Korea Health Industry Development Institute (KHIDI)","award":["2021R1A2C201052312"],"award-info":[{"award-number":["2021R1A2C201052312"]}]},{"name":"National Research Foundation of Korea (NRF)","award":["HI16C1559"],"award-info":[{"award-number":["HI16C1559"]}]},{"name":"National Research Foundation of Korea (NRF)","award":["2021R1A2C201052312"],"award-info":[{"award-number":["2021R1A2C201052312"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Stem cell therapies hold great promise as alternative treatments for incurable optic nerve disorders. Although mesenchymal stem cells exhibit various tissue regeneration and recovery capabilities that may serve as valuable therapies, the clinical applications remain limited. Thus, we investigated the utility of extracellular vesicles (EVs) from human placenta-derived mesenchymal stem cells (hPSCs) in this context. Hypoxically preconditioned hPSCs (HPPSCs) were prepared via short-term incubation under 2.2% O2 and 5.5% CO2. The EVs were then isolated. R28 cells (retinal precursor cells) were exposed to CoCl2 and treated with EVs for 24 h. Cell proliferation and regeneration were measured using a BrdU assay and immunoblotting; ATP quantification revealed the extent of the mitochondrial function. The proteome was determined via liquid chromatography-tandem mass spectroscopy. Differentially expressed proteins (DEPs) were detected and their interactions identified. HPPSC_EVs functions were explored using animal models of optic nerve compression. HPPSC_EVs restored cell proliferation and mitochondrial quality control in R28 cells damaged by CoCl2. We identified DEPs (p &lt; 0.05) that aided recovery. The mitochondrial DEPs included LONP1; PARK7; VDAC1, 2, and 3; HSPD1; and HSPA9. EVs regulated the levels of mitophagic proteins in R28 cells injured by hypoxia; the protein levels did not increase in LONP1 knockdown cells. LONP1 is a key mediator of the mitophagy that restores mitochondrial function after hypoxia-induced optic nerve injury.<\/jats:p>","DOI":"10.3390\/cells11233720","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T02:55:51Z","timestamp":1669172151000},"page":"3720","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["The Role of Extracellular Vesicles in Optic Nerve Injury: Neuroprotection and Mitochondrial Homeostasis"],"prefix":"10.3390","volume":"11","author":[{"given":"Mira","family":"Park","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, CHA Bundang Medical Center, CHA University, Seongnam 13496, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Ah","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, CHA Bundang Medical Center, CHA University, Seongnam 13496, 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\/0000-0002-8832-6587","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 Bundang Medical Center, CHA University, Seongnam 13496, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3362","DOI":"10.1007\/s12035-020-01965-8","article-title":"Hypoxia-Preconditioned Placenta-Derived Mesenchymal Stem Cells Rescue Optic Nerve Axons Via Differential Roles of Vascular Endothelial Growth Factor in an Optic Nerve Compression Animal Model","volume":"57","author":"Kwon","year":"2020","journal-title":"Mol. 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