Melatonin receptor agonist ramelteon alleviates experimental acute ocular inflammation via HIF-1?/VEGF/E-NOS signaling

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dc.authorid0000-0002-0065-4384
dc.authorid0000-0001-5204-3131
dc.contributor.authorSofu, Gulsah Usta
dc.contributor.authorErzurumlu, Yalcin
dc.contributor.authorKaraca, Umut
dc.contributor.authorCandan, Ibrahim Aydin
dc.contributor.authorSavran, Mehtap
dc.contributor.authorAsci, Halil
dc.contributor.authorHasseyid, Nursel
dc.date.accessioned2026-01-24T12:29:09Z
dc.date.available2026-01-24T12:29:09Z
dc.date.issued2023
dc.departmentAlanya Alaaddin Keykubat Üniversitesi
dc.description.abstractPurpose: Ramelteon (RML) is a potent, selective agonist of the high-affinity melatonin receptor 1 and 2 receptors. In addition, RML is known to have antioxidant and anti-inflammatory effects. In this study, we aimed to investigate the effects of RML on HIF-1 alpha, VEGF and e-NOS signaling pathway in a rat model of endotoxin-induced uveitis (EIU). Methods: Twenty-eight Wistar albino rats were divided into 4 groups as controls, lypopolysaccharide (LPS) group (5 mg/kg i.p.), LPS + RML group (5 mg/kg i.p and 8 mg/kg orally, respectively) and RML group (8 mg/kg orally). EIU was induced by a single intraperitoneal LPS injection. Histopathological and genetical analyses were performed. Results: In histopathological analysis, LPS caused mild anterior uveitis characterized by increased surface area of iris leaflets and ciliary body due to edema, mild to moderate congestion, and inflammatory infiltrate 6 h following the injection. The pathological findings were reduced by RML. Higher inflammation levels seen in LPS group were significantly reduced in LPS + RML group. Also, HIF-1 alpha, eNOS and VEGF expressions increased in LPS and decreased in LPS + RML group. Conclusion: RML treatment reversed the changes in the HIF-1 alpha /eNOS/ VEGF signaling pathway in LPS-induced uveitis in rats, preventing the progression of the damage and showed positive effects.
dc.description.sponsorshipScientific Research Projects Coordination Unit of Suleyman Demirel University [TSG-2021-8304]
dc.description.sponsorshipThe author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by the Scientific Research Projects Coordination Unit of Suleyman Demirel University with project code TSG-2021-8304.
dc.identifier.doi10.1177/11206721221123878
dc.identifier.endpage1025
dc.identifier.issn1120-6721
dc.identifier.issn1724-6016
dc.identifier.issue2
dc.identifier.scopus2-s2.0-85138238170
dc.identifier.scopusqualityQ2
dc.identifier.startpage1018
dc.identifier.urihttps://doi.org/10.1177/11206721221123878
dc.identifier.urihttps://hdl.handle.net/20.500.12868/5136
dc.identifier.volume33
dc.identifier.wosWOS:000849906400001
dc.identifier.wosqualityQ4
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherSage Publications Ltd
dc.relation.ispartofEuropean Journal of Ophthalmology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WoS_20260121
dc.subjectRamelteon
dc.subjectmelatonin analog
dc.subjectendotoxin-induced uveitis
dc.subjectinflammation
dc.subjectHIF 1 alpha
dc.titleMelatonin receptor agonist ramelteon alleviates experimental acute ocular inflammation via HIF-1?/VEGF/E-NOS signaling
dc.typeArticle

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