COCO/DAND5 inhibits developmental and pathological ocular angiogenesis.
COCO
angiogenesis
energy metabolism
ocular pathologies
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
05 03 2021
05 03 2021
Historique:
received:
21
01
2020
revised:
22
12
2020
accepted:
24
12
2020
pubmed:
16
2
2021
medline:
26
10
2021
entrez:
15
2
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33587337
doi: 10.15252/emmm.202012005
pmc: PMC7933934
doi:
Substances chimiques
DAND5 protein, human
0
Intercellular Signaling Peptides and Proteins
0
Vascular Endothelial Growth Factor A
0
Banques de données
GEO
['GSE160099']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12005Subventions
Organisme : CIHR
ID : FRN 363540
Pays : Canada
Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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