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


USTA SOFU G., ERZURUMLU Y., KARACA U., Candan I. A., SAVRAN M., AŞCI H., ...Daha Fazla

European Journal of Ophthalmology, cilt.33, sa.2, ss.1018-1025, 2023 (SCI-Expanded) identifier identifier

  • 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.