Dexmedetomidine preconditioning protects against retinal ischemia/reperfusion injury and inhibits inflammation response via toll-like receptor 4 (TLR4) pathway

Biomed Pharmacother. 2017 Sep:93:1018-1024. doi: 10.1016/j.biopha.2017.06.050. Epub 2017 Jul 15.

Abstract

Background: Retinal ischemia/reperfusion (I/R) injury is one of significant cause of visual dysopia and causes inflammatory response. Dexmedetomidine is widely applied to general/local anaesthesia and has been reported to have extensive anti-inflammatory effect. However, the role of dexmedetomidine in retinal I/R injury is currently unknown. This study investigates the effect of dexmedetomidine preconditioning on retinal I/R injury and explore the related signal mechanism toll-like receptor 4 (TLR4) pathway.

Methods: Retinal I/R injury model were established with SD rats through periocular injection. Retinal damage was quantified by measuring the thickness of retinal layers, cell counts of retinal ganglion cells (RGCs) and electroretinography (ERG). Apoptosis of retinal cell was detected by TUNEL assay. Protein and mRNA expression of glial fibrillary acidic protein (GFAP) were measured by western blot and real-time quantitate PCR. Bax, Bcl-2 and nuclear factor-κB (NF-κB) in retinas were detected by western blot.

Results: ERG and HE staining showed that dexmedetomidine preconditioning significantly inhibited the histologic damage induced by I/R injury, which expresses apparent concentration dependent. TUNEL demonstrated that apoptosis of retinal cells were reduced by dexmedetomidine. The expression of NF-κB and GFAP were decreased compared I/R blank group.

Conclusion: Dexmedetomidine preconditioning suppresses retinal I/R injury and shows effective anti-inflammatory effect by inhibiting TLR4/NF-κB expression.

Keywords: Anti-inflammatory; Dexmedetomidine; Nuclear factor-κB; Retinal ischemia/reperfusion; Toll-like receptor 4.

MeSH terms

  • Animals
  • Dexmedetomidine / administration & dosage*
  • Hypnotics and Sedatives / administration & dosage
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / metabolism
  • Ischemic Preconditioning / methods*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / prevention & control*
  • Retina / drug effects
  • Retina / metabolism
  • Retinal Vessels / drug effects*
  • Retinal Vessels / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Toll-Like Receptor 4 / antagonists & inhibitors*
  • Toll-Like Receptor 4 / biosynthesis

Substances

  • Hypnotics and Sedatives
  • Inflammation Mediators
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Dexmedetomidine