Suppression of retinal neovascularization by intravitreal injection of cryptotanshinone

Biochem Biophys Res Commun. 2024 Aug 6:720:150065. doi: 10.1016/j.bbrc.2024.150065. Epub 2024 May 7.

Abstract

Neovascular eye diseases, including proliferative diabetic retinopathy and retinopathy of prematurity, is a major cause of blindness. Laser ablation and intravitreal anti-VEGF injection have shown their limitations in treatment of retinal neovascularization. Identification of a new therapeutic strategies is in urgent need. Our study aims to assess the effects of Cryptotanshinone (CPT), a natural compound derived from Salvia miltiorrhiza Bunge, in retina neovascularization and explore its potential mechanism. Our study demonstrated that CPT did not cause retina tissue toxicity at the tested concentrations. Intravitreal injections of CPT reduced pathological angiogenesis and promoted physical angiogenesis in oxygen-induced retinopathy (OIR) model. CPT improve visual function in OIR mice and reduced cell apoptosis. Moreover, we also revealed that CPT diminishes the expression of inflammatory cytokines in the OIR retina. In vitro, the administration of CPT effectively inhibited endothelial cells proliferation, migration, sprouting, and tube formation induced by the stimulation of human retinal vascular endothelial cells (HRVECs) with VEGF165. Mechanistically, CPT blocking the phosphorylation of VEGFR2 and downstream targeting pathway. After all, the findings demonstrated that CPT exhibits potent anti-angiogenic and anti-inflammatory effects in OIR mice, and it has therapeutic potential for the treatment of neovascular retinal diseases.

Keywords: Angiogenesis; Cryptotanshinone; Oxygen induced retinopathy; STAT3; VEGFR2.

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Humans
  • Intravitreal Injections*
  • Mice
  • Mice, Inbred C57BL*
  • Phenanthrenes* / administration & dosage
  • Phenanthrenes* / pharmacology
  • Retina / drug effects
  • Retina / metabolism
  • Retina / pathology
  • Retinal Neovascularization* / drug therapy
  • Retinal Neovascularization* / metabolism
  • Retinal Neovascularization* / pathology

Substances

  • cryptotanshinone
  • Phenanthrenes
  • Angiogenesis Inhibitors