Intravitreal injection of anti-miRs against miR-142-3p reduces angiogenesis and microglia activation in a mouse model of laser-induced choroidal neovascularization.
Aging (Albany NY)
; 13(9): 12359-12377, 2021 05 05.
Article
in En
| MEDLINE
| ID: mdl-33952723
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Choroidal Neovascularization
/
MicroRNAs
/
Lasers
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Aging (Albany NY)
Journal subject:
GERIATRIA
Year:
2021
Type:
Article
Affiliation country:
Belgium