{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:24:05Z","timestamp":1788452645393,"version":"build-2803163510"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T00:00:00Z","timestamp":1671148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016808","name":"Natural Science Foundation of Xiamen City","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016808","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Purpose:<\/jats:bold> The purpose of this study was to explore the potential underlying mechanism of anti-vascular effects of peroxisome proliferator\u2013activated receptor \u03b1 (PPAR\u03b1) agonist fenofibrate against corneal neovascularization (CNV) through the changes of lipid metabolism during CNV.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> A suture-induced CNV model was established and the clinical indications were evaluated from day 1 to day 7. Treatments of vehicle and fenofibrate were performed for 5\u00a0days after suture and the CNV areas were compared among the groups. The eyeballs were collected for histological analysis, malondialdehyde (MDA) measurement, terminal deoxynucleotidyl transferase 2\u2032-deoxyuridine 5\u2032-triphosphate nick end labeling (TUNEL) staining, western blot, quantitative real-time PCR (qRT-PCR) assays and immunohistochemical (IHC) staining to elucidate pathological changes and the underlying mechanism.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Lipi-Green staining and MDA measurement showed that lipid deposition and peroxidation were increased in the CNV cornea while the expression of long-chain acyl-coenzyme A synthetase 1 (ACSL1), carnitine palmitoyltransterase 1A(CPT1A) and medium-chain acyl-coenzyme A dehydrogenase (ACADM), which are key enzymes of fatty acid \u03b2-oxidation (FAO) and targeted genes of peroxisome proliferator-activated receptor alpha (PPAR\u03b1) pathway, were decreased in CNV cornea. Fenofibrate suppressed lipid accumulation and peroxidation damage in the CNV cornea. Fenofibrate upregulated the expression levels of PPAR\u03b1, ACSL1, CPT1A, and ACADM compared with vehicle group. IHC staining indicated that fenofibrate also decreased the expression of VEGFa, VEGFc, TNF\u03b1, IL1\u03b2 and CD68.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Disorder of lipid metabolism may be involved in the formation of suture-induced CNV and fenofibrate played anti-neovascularization and anti-inflammatory roles on cornea by regulating the key enzymes of lipid metabolism and ameliorating lipid peroxidation damage of cornea through PPAR\u03b1 signaling pathway.<\/jats:p>","DOI":"10.3389\/fphar.2022.1000254","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T07:03:25Z","timestamp":1671174205000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Fenofibrate suppresses corneal neovascularization by regulating lipid metabolism through PPAR\u03b1 signaling pathway"],"prefix":"10.3389","volume":"13","author":[{"given":"Tong","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linfangzi","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiang","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxiong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuguo","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoqiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"36","DOI":"10.2337\/db12-1223","article-title":"Direct effects of PPAR\u03b1 agonists on retinal inflammation and angiogenesis may explain how fenofibrate lowers risk of severe proliferative diabetic retinopathy","volume":"62","author":"Abcouwer","year":"2013","journal-title":"Diabetes"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1016\/j.ophtha.2010.01.039","article-title":"Corneal neovascularization as a risk factor for graft failure and rejection after keratoplasty: An evidence-based meta-analysis","volume":"117","author":"Bachmann","year":"2010","journal-title":"Ophthalmology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1177\/1120672119874947","article-title":"Regression of corneal neovascularization: Adiponectin versus bevacizumab eye drops","volume":"31","author":"Baradaran-Rafii","year":"2021","journal-title":"Eur. 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