Open AccessCOCO/DAND5 inhibits developmental and pathological ocular angiogenesis
Author(s) -
Popovic Natalija,
Hooker Erika,
Barabino Andrea,
Flamier Anthony,
Provost Frédéric,
Buscarlet Manuel,
Bernier Gilbert,
Larrivée Bruno
Publication year - 2021
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202012005
Subject(s) - angiogenesis , macular degeneration , choroidal neovascularization , retinopathy of prematurity , neovascularization , coco , cancer research , vascular endothelial growth factor a , medicine , retinal , vascular endothelial growth factor , biology , ophthalmology , vegf receptors , genetics , gestational age , pregnancy , artificial intelligence , computer science
Neovascularization contributes to multiple visual disorders including age‐related macular degeneration (AMD) and retinopathy of prematurity. Current therapies for treating ocular angiogenesis are centered on the inhibition of vascular endothelial growth factor (VEGF). While clinically effective, some AMD patients are refractory or develop resistance to anti‐VEGF therapies and concerns of increased risks of developing geographic atrophy following long‐term treatment have been raised. Identification of alternative pathways to inhibit pathological angiogenesis is thus important. We have identified a novel inhibitor of angiogenesis, COCO, a member of the Cerberus‐related DAN protein family. We demonstrate that COCO inhibits sprouting, migration and cellular proliferation of cultured endothelial cells. Intravitreal injections of COCO inhibited retinal vascularization during development and in models of retinopathy of prematurity. COCO equally abrogated angiogenesis in models of choroidal neovascularization. Mechanistically, COCO inhibited TGFβ and BMP pathways and altered energy metabolism and redox balance of endothelial cells. Together, these data show that COCO is an inhibitor of retinal and choroidal angiogenesis, possibly representing a therapeutic option for the treatment of neovascular ocular diseases.