An Endostatin-lentivirus (ES-LV)-EPC gene therapy agent for suppression of neovascularization in oxygen-induced retinopathy rat model

BMC Mol Cell Biol. 2020 Jul 29;21(1):57. doi: 10.1186/s12860-020-00301-1.

Abstract

Background: Transplantation of gene transfected endothelial progenitor cells (EPCs) has provided novel methods for tumor neovascularization therapy but not for ocular disease therapy. This study aimed to investigate the efficacy of endostatin transfected EPCs in retinal neovascularization therapy.

Results: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) showed the high expression of endostatin in endostatin-lentivirus-EPCs. The neovascularization leakage area and the number of preretinal neovascular cell nuclei were significantly decreased in the endostatin-lentivirus and endostatin-lentivirus-EPC groups, and the effects of these two treatments on inhibiting retinal neovascularization were almost the same. These two groups also showed the greater retinal distribution of endostatin. Intravitreal injections of endostatin-lentivirus-EPCs inhibited retinal neovascularization, vascular endothelial growth factor (VEGF) and CD31 expression, and increased endostatin expression in vivo. Endostatin-lentivirus-EPCs targeted and prevented pathologic retinal neovascularization.

Conclusions: Gene-combined EPCs represent a potential new therapeutic agent for the treatment of neovascular eye diseases.

Keywords: Endostatin; Endothelial progenitor cells; Gene therapy; Retinal neovascularization.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Endostatins / genetics*
  • Endostatins / therapeutic use*
  • Endothelial Progenitor Cells / metabolism
  • Fluorescein Angiography
  • Fundus Oculi
  • Genetic Therapy*
  • Lentivirus / genetics*
  • Oxygen
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • Retinal Neovascularization / therapy*
  • Vascular Endothelial Growth Factors / metabolism

Substances

  • Endostatins
  • Platelet Endothelial Cell Adhesion Molecule-1
  • RNA, Messenger
  • Vascular Endothelial Growth Factors
  • Oxygen