{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:01:17Z","timestamp":1785416477282,"version":"3.56.0"},"reference-count":59,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471048, 82271045"],"award-info":[{"award-number":["82471048, 82271045"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82471048, 82271045"],"award-info":[{"award-number":["82471048, 82271045"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Shenzhen Science and Technology Program","award":["JCYJ20240813145510014"],"award-info":[{"award-number":["JCYJ20240813145510014"]}]},{"name":"Xiamen Municipal Health and Medical Guidance Projects","award":["3502Z20224ZD1018"],"award-info":[{"award-number":["3502Z20224ZD1018"]}]},{"name":"Fujian Provincial Natural Science Foundation Projects","award":["2022J05302"],"award-info":[{"award-number":["2022J05302"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Purpose: Chiglitazar (Chi) is a pan-peroxisome proliferator-activated receptor (PPAR) agonist with reported anti-oxidative effects in metabolic disorders. In this study, we investigate its therapeutic effects and potential mechanisms in corneal neovascularization (CNV). Methods: Scratch-wound and tube formation assays in human umbilical vein endothelial cells (HUVECs) were performed to evaluate the effects of Chi under recombinant human vascular endothelial growth factor (VEGF) stimulation. An oxidative stress model was established in human corneal epithelial cells (HCEs), and intracellular reactive oxygen species (ROS) levels were quantified by flow cytometry. A corneal alkali burn mouse model of CNV was established. Chi was then administered and compared with vehicle, pioglitazone, or fenofibrate. Corneal epithelial healing and neovascularization were assessed. Public drug\u2013disease\u2013target resources were integrated with RNA-seq data and single-cell transcriptomes to prioritize Chi-associated targets and pathways, which were examined by immunofluorescence, RT-PCR, and Western blotting. Ocular safety was evaluated by comprehensive ophthalmic evaluation. Results: Chi significantly inhibited migration and tube formation in VEGF-induced HUVECs, and flow cytometry confirmed effective ROS reduction. In vivo, Chi markedly improved corneal conditions compared with the vehicle and showed efficacy comparable to or superior to selective PPAR-\u03b1\/\u03b3 agonists, depending on the outcome measures. Bioinformatic analyses predicted PPAR-\u03b3 as the dominant isoform, with PPAR-\u03b1 secondary and PPAR-\u03b4 appearing less prominent, collectively implicating oxidative stress and VEGF pathways. Immunofluorescence verified PPAR-\u03b3 activation, predominantly localized to the corneal epithelium. RT-PCR and Western blotting supported activation of antioxidant pathways and suppression of angiogenic signals, with Western blotting confirming PPAR-\u03b3 and PPAR-\u03b1 activation, whereas PPAR-\u03b4 activation appeared less evident under the present conditions. Ocular examinations demonstrated a favorable safety profile. Conclusions: Chi primarily activates PPAR-\u03b3 and PPAR-\u03b1, producing antioxidant and anti-angiogenic benefits, supporting its potential as a multi-target PPAR therapy for CNV.<\/jats:p>","DOI":"10.3390\/antiox15040449","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T15:14:43Z","timestamp":1775142883000},"page":"449","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chiglitazar Activates PPAR-\u03b1\/\u03b3 to Suppress Oxidative Stress and Angiogenesis in Corneal Neovascularization"],"prefix":"10.3390","volume":"15","author":[{"given":"Tao","family":"Tao","sequence":"first","affiliation":[{"name":"Eye Institute & Affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyuan","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Digestive Disease, Institute for Microbial Ecology, School of Medicine, Xiamen University, Xiamen 361004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruifeng","family":"Li","sequence":"additional","affiliation":[{"name":"Eye Institute & Affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The First Affiliated Hospital, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The First Affiliated Hospital, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Eye Institute & Affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Eye Institute & Affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Digestive Disease, Institute for Microbial Ecology, School of Medicine, Xiamen University, Xiamen 361004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Eye Institute & Affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Wang","sequence":"additional","affiliation":[{"name":"Eye Institute & Affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0449-3709","authenticated-orcid":false,"given":"Cheng","family":"Li","sequence":"additional","affiliation":[{"name":"Eye Institute & Affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen 361102, China"},{"name":"Huaxia Eye Hospital of Quanzhou, Quanzhou 362000, China"},{"name":"Shen Zhen Research Institute, Xiamen University, Shenzhen 518057, China"},{"name":"Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4863","DOI":"10.1167\/iovs.14-14023","article-title":"Serine Proteinase Inhibitor SERPINA3K Suppresses Corneal Neovascularization via Inhibiting Wnt Signaling and VEGF","volume":"55","author":"Zhou","year":"2014","journal-title":"Investig. 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