Melatonin receptor agonist ramelteon alleviates experimental acute ocular inflammation via HIF-1Α/VEGF/E-NOS signaling
European Journal of Ophthalmology, cilt.33, sa.2, ss.1018-1025, 2023 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 33 Sayı: 2
- Basım Tarihi: 2023
- Doi Numarası: 10.1177/11206721221123878
- Dergi Adı: European Journal of Ophthalmology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CAB Abstracts, EMBASE, MEDLINE
- Sayfa Sayıları: ss.1018-1025
- Anahtar Kelimeler: endotoxin-induced uveitis, HIF 1α, inflammation, melatonin analog, Ramelteon
- İstanbul Yeni Yüzyıl Üniversitesi Adresli: Hayır
Özet
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.