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Gene therapy offers a promising alternative, but is hindered by the limitations in existing delivery systems and the scarcity of validated molecular targets capable of reversing core pathophysiology. To address this, we first employed multi\u2010omics analysis and identified FOXO1 as a central and under\u2010explored therapeutic target for corneal endothelial dysfunction. In vivo FOXO1 overexpression effectively improved corneal endothelial function by preserving mitochondria\u2010associated endoplasmic reticulum membrane integrity and mitochondrial Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    homeostasis, yet its therapeutic potential was limited by low transfection efficiency. To overcome this, we engineered an AAV\u2010\n                    <jats:italic>Foxo1<\/jats:italic>\n                    delivery system using a viscous choline chloride\u2010fructose\u2010based deep eutectic solvent (DES) as the carrier. The DES\u2010AAV\u2010\n                    <jats:italic>Foxo1<\/jats:italic>\n                    delivery system exhibited good biocompatibility, significantly prolonged anterior chamber retention, and enhanced transfection efficiency in corneal endothelial cells compared to conventional AAV delivery. Animal experiments confirmed that it effectively improved corneal endothelial pump activity and mitigates endothelial dysfunction in type 1 diabetes mellitus and Fuchs endothelial corneal dystrophy mouse models. Our findings demonstrated the therapeutic potential of DES\u2010AAV\u2010\n                    <jats:italic>Foxo1<\/jats:italic>\n                    delivery system for corneal endothelial disorders.\n                  <\/jats:p>","DOI":"10.1002\/advs.75464","type":"journal-article","created":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T21:04:13Z","timestamp":1777842253000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Viscous DES\u2010AAV\u2010\n                    <i>Foxo1<\/i>\n                    Delivery System With High Transfection Efficiency for the Treatment of Corneal Endothelial Dysfunction by Restoring Mitochondria\u2010ER Contacts"],"prefix":"10.1002","volume":"13","author":[{"given":"Hongran","family":"Zhao","sequence":"first","affiliation":[{"name":"Eye Institute of Shandong First Medical University  Qingdao China"},{"name":"State Key Laboratory Cultivation Base Shandong Key Laboratory of 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