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| Status |
Public on Dec 22, 2020 |
| Title |
COCO/DAND5 inhibits developmental and pathological ocular angiogenesis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Neovascularization contributes to multiple visual disorders including age-related macular degeneration (AMD). 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 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/DAND5, a member of the Cerberus-related DAN 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 and AMD. COCO equally abrogated angiogenesis in choroid explants and in a model of choroidal neovascularization. Mechanistically, COCO inhibited the expression of TGFβ and BMP pathwaysand altered ATP production, glucose uptake 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.
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| Overall design |
HUVEC cells treated with or without COCO for 16 hours, in quadruplicate. Transcriptomic analysis using Ion AmpliSeq Transcriptome Human Gene Expression Kit (Thermo Fisher Scientific) according to manufacturer's instructions.
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| Contributor(s) |
Larrivée B, Popovic N, Hooker E, Barabino A, Flamier A, Provost F, Bernier G, Buscarlet M |
| Citation(s) |
33587337 |
| |
| Submission date |
Oct 26, 2020 |
| Last update date |
Mar 23, 2021 |
| Contact name |
Bruno Larrivée |
| E-mail(s) |
bruno.larrivee@umontreal.ca
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| Organization name |
Hôpital Maisonneuve-Rosemont
|
| Street address |
5415 Boul. L'Assomption
|
| City |
Montreal |
| State/province |
Quebec |
| ZIP/Postal code |
H1T2M4 |
| Country |
Canada |
| |
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| Platforms (1) |
| GPL17303 |
Ion Torrent Proton (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA671828 |
| SRA |
SRP288569 |
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