Melatonin receptor agonist ramelteon alleviates experimental acute ocular inflammation via HIF-1Α/VEGF/E-NOS signaling. Issue 2 (March 2023)

• Record Type: Journal Article
• Authors: Usta Sofu, Gulsah; Erzurumlu, Yalcın; Karaca, Umut; Candan, Ibrahim Aydın; Savran, Mehtap; Asci, Halil; Hasseyid, Nursel
• Is Part Of: European journal of ophthalmology. Volume 33:Issue 2(2023)
• Page Start: 1018
• Page End: 1025
• Publication Date: 2023-03
• Subjects: Ramelteon -- melatonin analog -- endotoxin-induced uveitis -- inflammation -- HIF 1α; Ophthalmology -- Periodicals; Eye -- Diseases -- Periodicals; 617.7005
• DOI: 10.1177/11206721221123878
• Languages: English
• ISSNs: 1120-6721

Abstract

Purpose: 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-1α, 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 α, eNOS and VEGF expressions increased in LPS and decreased in LPS + RML group. Conclusion: RML treatment reversed the changes in the HIF-1α /eNOS/ VEGF signaling pathway in LPS-induced uveitis in rats, preventing the progression of the damage and showed positive effects.