{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:13:14Z","timestamp":1791267194138,"version":"4.1.0"},"reference-count":64,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T00:00:00Z","timestamp":1699833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004080","name":"Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["HN22C0190"],"award-info":[{"award-number":["HN22C0190"]}],"id":[{"id":"10.13039\/501100004080","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Elevated intraocular pressure (IOP) in glaucoma causes retinal ganglion cell (RGC) loss and damage to the optic nerve. Although IOP is controlled pharmacologically, no treatment is available to restore retinal and optic nerve function. In this paper, we aimed to develop a novel gene therapy for glaucoma using an AAV2-based thioredoxin 2 (Trx2)-exoenzyme C3 transferase (C3) fusion protein expression vector (scAAV2-Trx2-C3). We evaluated the therapeutic effects of this vector in vitro and in vivo using dexamethasone (DEX)-induced glaucoma models. We found that scAAV2-Trx2-C3-treated HeLa cells had significantly reduced GTP-bound active RhoA and increased phosphor-cofilin Ser3 protein expression levels. scAAV2-Trx2-C3 was also shown to inhibit oxidative stress, fibronectin expression, and alpha-SMA expression in DEX-treated HeLa cells. NeuN immunostaining and TUNEL assay in mouse retinal tissues was performed to evaluate its neuroprotective effect upon RGCs, whereas changes in mouse IOP were monitored via rebound tonometer. The present study showed that scAAV2-Trx2-C3 can protect RGCs from degeneration and reduce IOP in a DEX-induced mouse model of glaucoma, while immunohistochemistry revealed that the expression of fibronectin and alpha-SMA was decreased after the transduction of scAAV2-Trx2-C3 in murine eye tissues. Our results suggest that AAV2-Trx2-C3 modulates the outflow resistance of the trabecular meshwork, protects retinal and other ocular tissues from oxidative damage, and may lead to the development of a gene therapeutic for glaucoma.<\/jats:p>","DOI":"10.3390\/ijms242216253","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T08:35:52Z","timestamp":1699864552000},"page":"16253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["scAAV2-Mediated Expression of Thioredoxin 2 and C3 Transferase Prevents Retinal Ganglion Cell Death and Lowers Intraocular Pressure in a Mouse Model of Glaucoma"],"prefix":"10.3390","volume":"24","author":[{"given":"Hee Jong","family":"Kim","sequence":"first","affiliation":[{"name":"Institute of New Drug Development Research, Cdmogen Co., Ltd., Seoul 05855, Republic of Korea"},{"name":"Cdmogen Co., Ltd., Cheongju 28577, Republic of 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Medicine, University of Ulsan, Seoul 05505, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5125-7170","authenticated-orcid":false,"given":"Ko Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Republic of Korea"},{"name":"Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Kwon","family":"Kim","sequence":"additional","affiliation":[{"name":"Institute of New Drug Development Research, Cdmogen Co., Ltd., Seoul 05855, Republic of Korea"},{"name":"Cdmogen Co., Ltd., Cheongju 28577, Republic of 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