Inhibitory effect of miR‑182‑5p on retinal neovascularization by targeting angiogenin and BDNF

Mol Med Rep. 2022 Feb;25(2):61. doi: 10.3892/mmr.2021.12577. Epub 2021 Dec 22.

Abstract

Retinal neovascularization (RNV) is a type of serious vision‑threating disease, commonly induced by hypoxia of ischemic retinopathy, which happens in various ocular diseases including diabetic retinopathy and retinopathy of prematurity. In clinical work, anti‑VEGF therapy is the preferred strategy for treating RNV. However, not all cases are sensitive to anti‑VEGF injection. It is urgent and necessary to develop novel targets for inhibiting neovascularization in ocular diseases. Angiogenin (ANG) and brain‑derived neurotrophic factor (BDNF) are implicated in angiogenesis, although their regulation and effects in RNV remain to be elucidated. microRNA (miRNA) is a type of small non‑coding RNA, which can modulate targets by degrading transcripts or inhibiting protein translation. In the present study, miRNA‑mediated modulation of ANG and BDNF was explored in an oxygen‑induced retinopathy mouse model and human retinal microvascular endothelial cells (HRECs) under hypoxia. The results showed that downregulation of miR‑182‑5p and upregulation of ANG and BDNF were found in vivo and in vitro. Overexpression of miR‑182‑5p suppressed the expression of ANG and BDNF significantly in HRECs under hypoxia. In addition, knockdown of ANG and BDNF by miR‑182‑5p transfection significantly improved hypoxia‑induced HRECs dysfunctions, including enhancing cell viability, reducing cell migration and improved tube integrity. In conclusion, miRNA‑dependent regulation on ANG and BDNF indicates a critical role in hypoxia‑induced retinal microvascular response. miR‑182‑5p‑based therapy can influence the expression of ANG and BDNF, which demonstrates the potential for treating RNV diseases.

Keywords: angiogenin; brain‑derived neurotrophic factor; hypoxia; microRNA; retinal neovascularization.

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Disease Models, Animal
  • Endothelial Cells / metabolism
  • Female
  • Gene Expression Regulation
  • Humans
  • Hypoxia / metabolism
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism*
  • Neovascularization, Pathologic / metabolism
  • Oxygen / metabolism
  • Pregnancy
  • Retinal Neovascularization / genetics
  • Retinal Neovascularization / metabolism*
  • Retinal Vessels
  • Ribonuclease, Pancreatic / metabolism*

Substances

  • Brain-Derived Neurotrophic Factor
  • MicroRNAs
  • Mirn182 microRNA, human
  • Mirn182 microRNA, mouse
  • BDNF protein, human
  • angiogenin
  • Ribonuclease, Pancreatic
  • Oxygen

Grants and funding

This study was funded by Changhai Hospital Teaching Research and Reform Project Fund in 2019 (grant no. CHJG2019012).