{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:55:49Z","timestamp":1788742549259,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2020,7,19]],"date-time":"2020-07-19T00:00:00Z","timestamp":1595116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K18859"],"award-info":[{"award-number":["19K18859"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Peroxisome proliferator-activated receptor alpha (PPAR\u03b1) and gamma (PPAR\u03b3) agonists have anti-inflammatory and anti-neovascularization effects, but few reports have tested the combination of PPAR\u03b1 and PPAR\u03b3 agonists. In this study, we investigated the therapeutic effects of ophthalmic solutions of agonists of PPAR\u03b1, PPAR\u03b3, and the combination in a rat corneal alkali burn model. After alkali injury, an ophthalmic solution of 0.05% fenofibrate (PPAR\u03b1 group), 0.1% pioglitazone (PPAR\u03b3 group), 0.05% fenofibrate + 0.1% pioglitazone (PPAR\u03b1+\u03b3 group), or vehicle (vehicle group) was topically instilled onto the rat\u2019s cornea twice a day. After instillation, upregulation was seen of PPAR mRNA corresponding to each agonist group. Administration of agonists for PPAR\u03b1, PPAR\u03b3, and PPAR\u03b1+\u03b3 suppressed inflammatory cells, neovascularization, and fibrotic changes. In addition, the PPAR\u03b3 agonist upregulated M2 macrophages, which contributed to wound healing, whereas the PPAR\u03b1 agonist suppressed immature blood vessels in the early phase. Administration of PPAR\u03b1+\u03b3 agonists showed therapeutic effects in corneal wound healing, combining the characteristics of both PPAR\u03b1 and PPAR\u03b3 agonists. The results indicate that the combination of PPAR\u03b1 and \u03b3 agonists may be a new therapeutic strategy.<\/jats:p>","DOI":"10.3390\/ijms21145093","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T06:08:17Z","timestamp":1595225297000},"page":"5093","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Combination of Peroxisome Proliferator-Activated Receptor (PPAR) Alpha and Gamma Agonists Prevents Corneal Inflammation and Neovascularization in a Rat Alkali Burn Model"],"prefix":"10.3390","volume":"21","author":[{"given":"Yuji","family":"Nakano","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Nippon Medical School, Tokyo 113-8602, Japan"},{"name":"Department of Analytic Human Pathology, Nippon Medical School, Tokyo 113-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1006-4430","authenticated-orcid":false,"given":"Takeshi","family":"Arima","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Nippon Medical School, Tokyo 113-8602, Japan"},{"name":"Department of Analytic Human Pathology, Nippon Medical School, Tokyo 113-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaro","family":"Tobita","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Nippon Medical School, Tokyo 113-8602, Japan"},{"name":"Department of Analytic Human Pathology, Nippon Medical School, Tokyo 113-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Uchiyama","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Nippon Medical School, Tokyo 113-8602, Japan"},{"name":"Department of Analytic Human Pathology, Nippon Medical School, Tokyo 113-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4364-9251","authenticated-orcid":false,"given":"Akira","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Analytic Human Pathology, Nippon Medical School, Tokyo 113-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Nippon Medical School, Tokyo 113-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0039-6257(96)00007-0","article-title":"Chemical injuries of the eye: Current concepts in pathophysiology and therapy","volume":"41","author":"Wagoner","year":"1997","journal-title":"Surv. 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