Intravitreal injection of anti-miRs against miR-142-3p reduces angiogenesis and microglia activation in a mouse model of laser-induced choroidal neovascularization

Quentin Roblain, Thomas Louis, Cassandre Yip, Louis Baudin, Ingrid Struman, Vincenza Caolo, Vincent Lambert, Julie Lecomte, Agnes Noel*, Stephane Heymans

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Age-related macular degeneration (AMD) is a worldwide leading cause of blindness affecting individuals over 50 years old. The most aggressive form, wet AMD, is characterized by choroidal neovascularization (CNV) and inflammation involving microglia recruitment. By using a laser-induced CNV mouse model, we provide evidence for a key role played by miR-142-3p during CNV formation. MiR-142-3p was overexpressed in murine CNV lesions and its pharmacological inhibition decreased vascular and microglia densities by 46% and 30%, respectively. Consistently, miR-142-3p overexpression with mimics resulted in an increase of 136% and 126% of blood vessels and microglia recruitment. Interestingly, miR-142-3p expression was linked to the activation state of mouse microglia cells as determined by morphological analysis (cell solidity) through a computational method. In vitro, miR-142-3p overexpression in human microglia cells (HMC3) modulated microglia activation, as shown by CD68 levels. Interestingly, miR142-3p modulation also regulated the production of VEGF-A, the main pro-angiogenic factor. Together, these data strongly support the unprecedented importance of miR-142-3p-dependent vascular-inflammation axis during CNV progression, through microglia activation.

Original languageEnglish
Pages (from-to)12359-12377
Number of pages19
JournalAging
Volume13
Issue number9
DOIs
Publication statusPublished - 15 May 2021

Keywords

  • EXPRESSION
  • KEY
  • MACULAR DEGENERATION
  • MICRORNA-142
  • REGULATOR
  • age-related macular degeneration
  • angiogenesis
  • inflammation
  • miR-142-3p
  • microglia

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