Irisin Attenuates Pathological Neovascularization in Oxygen-Induced Retinopathy Mice

Invest Ophthalmol Vis Sci. 2022 Jun 1;63(6):21. doi: 10.1167/iovs.63.6.21.

Abstract

Purpose: Abnormal angiogenesis is a defining feature in a couple of ocular neovascular diseases. The application of anti-VEGFA therapy has achieved certain benefits in the clinic, accompanying side effects and poor responsiveness in many patients. The present study investigated the role of irisin in retinal neovascularization.

Methods: Western blot and quantitative PCR were used to determine irisin expression in the oxygen-induced retinopathy mice model. The pathological angiogenesis and inflammation index were examined after irisin administration. Primary retinal astrocytes were cultured and analyzed for VEGFA expression in vitro. Astrocyte-conditioned medium was collected for transwell assay and tube formation assay in human microvascular endothelial cells-1.

Results: Irisin was downregulated in the oxygen-induced retinopathy mice retinae. Additional irisin attenuated pathological angiogenesis, inflammation, and apoptosis in vivo. In vitro, irisin decreased astrocyte VEGFA production, and the conditioned medium suppressed human microvascular endothelial cells-1 migration. Last, irisin inhibited hypoxia-inducible factor-2α, nuclear factor-κB, and pNF-κB (Phospho-Nuclear Factor-κB) expression.

Conclusions: Irisin mitigates retinal pathological angiogenesis.

Chinese Abstract.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Culture Media, Conditioned / pharmacology
  • Disease Models, Animal
  • Endothelial Cells / metabolism
  • Fibronectins
  • Humans
  • Inflammation / pathology
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B
  • Neovascularization, Pathologic / drug therapy
  • Oxygen* / toxicity
  • Retinal Neovascularization* / metabolism

Substances

  • Culture Media, Conditioned
  • FNDC5 protein, mouse
  • Fibronectins
  • NF-kappa B
  • Oxygen