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miR‐30a‐5p inhibition promotes interaction of Fas + endothelial cells and FasL + microglia to decrease pathological neovascularization and promote physiological angiogenesis
Author(s) -
Murinello Salome,
Usui Yoshihiko,
Sakimoto Susumu,
Kitano Maki,
Aguilar Edith,
Friedlander H. Maura,
Schricker Amelia,
Wittgrove Carli,
Wakabayashi Yoshihiro,
Dorrell Michael I.,
Westenskow Peter D.,
Friedlander Martin
Publication year - 2019
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23543
Subject(s) - angiogenesis , biology , neovascularization , endothelial stem cell , microglia , cancer research , vascular endothelial growth factor a , apoptosis , microbiology and biotechnology , neurodegeneration , immunology , vascular endothelial growth factor , inflammation , pathology , medicine , disease , biochemistry , vegf receptors , in vitro
Ischemia‐induced angiogenesis contributes to various neuronal and retinal diseases, and often results in neurodegeneration and visual impairment. Current treatments involve the use of anti‐VEGF agents but are not successful in all cases. In this study we determined that miR‐30a‐5p is another important mediator of retinal angiogenesis. Using a rodent model of ischemic retinopathy, we show that inhibiting miR‐30a‐5p reduces neovascularization and promotes tissue repair, through modulation of microglial and endothelial cell cross‐talk. miR‐30a‐5p inhibition results in increased expression of the death receptor Fas and CCL2, to decrease endothelial cell survival and promote microglial migration and phagocytic function in focal regions of ischemic injury. Our data suggest that miR‐30a‐5p inhibition accelerates tissue repair by enhancing FasL–Fas crosstalk between microglia and endothelial cells, to promote endothelial cell apoptosis and removal of dead endothelial cells. Finally, we found that miR‐30a levels were increased in the vitreous of patients with proliferative diabetic retinopathy. Our study identifies a role for miR‐30a in the pathogenesis of neovascular retinal disease by modulating microglial and endothelial cell function, and suggests it may be a therapeutic target to treat ischemia‐mediated conditions.