Research Paper Volume 13, Issue 9 pp 12359—12377
Intravitreal injection of anti-miRs against miR-142-3p reduces angiogenesis and microglia activation in a mouse model of laser-induced choroidal neovascularization
- 1 Laboratory of Tumor and Development Biology, GIGA-Cancer, University of Liège, Liège, Belgium
- 2 Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
- 3 Molecular Angiogenesis Laboratory, GIGA-Cancer, University of Liège, Liège, Belgium
- 4 Ophthalmic Tissue Bank, Department of Ophthalmology, University Hospital of Liège, Sart-Tilman, Belgium
- 5 Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium
Received: December 5, 2020 Accepted: March 14, 2021 Published: May 5, 2021https://doi.org/10.18632/aging.203035
How to Cite
Copyright: © 2021 Roblain et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.