Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation.
Amacrine Cells
/ physiology
Animals
Blood-Retinal Barrier
/ drug effects
Bridged Bicyclo Compounds, Heterocyclic
/ pharmacology
Cholinergic Neurons
/ drug effects
Endothelial Cells
/ drug effects
Eye Proteins
/ metabolism
Mice
Neovascularization, Physiologic
/ physiology
Nerve Tissue Proteins
/ metabolism
Nicotinic Agonists
/ pharmacology
Oxygen
/ adverse effects
Pyridines
/ pharmacology
Retinal Diseases
Retinal Ganglion Cells
/ metabolism
Retinal Neovascularization
/ etiology
Tetrodotoxin
/ pharmacology
Vascular Endothelial Growth Factor A
/ metabolism
beta Catenin
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
06 06 2019
06 06 2019
Historique:
received:
25
07
2018
accepted:
26
04
2019
entrez:
8
6
2019
pubmed:
7
6
2019
medline:
18
6
2019
Statut:
epublish
Résumé
Blood vessels in the central nervous system (CNS) develop unique features, but the contribution of CNS neurons to regulating those features is not fully understood. We report that inhibiting spontaneous cholinergic activity or reducing starburst amacrine cell numbers prevents invasion of endothelial cells into the deep layers of the retina and causes blood-retinal-barrier (BRB) dysfunction in mice. Vascular endothelial growth factor (VEGF), which drives angiogenesis, and Norrin, a Wnt ligand that induces BRB properties, are decreased after activity blockade. Exogenous VEGF restores vessel growth but not BRB function, whereas stabilizing beta-catenin in endothelial cells rescues BRB dysfunction but not vessel formation. We further identify that inhibiting cholinergic activity reduces angiogenesis during oxygen-induced retinopathy. Our findings demonstrate that neural activity lies upstream of VEGF and Norrin, coordinating angiogenesis and BRB formation. Neural activity originating from specific neural circuits may be a general mechanism for driving regional angiogenesis and barrier formation across CNS development.
Identifiants
pubmed: 31171770
doi: 10.1038/s41467-019-10219-8
pii: 10.1038/s41467-019-10219-8
pmc: PMC6554348
doi:
Substances chimiques
Bridged Bicyclo Compounds, Heterocyclic
0
CTNNB1 protein, mouse
0
Eye Proteins
0
Ndph protein, mouse
0
Nerve Tissue Proteins
0
Nicotinic Agonists
0
Pyridines
0
Vascular Endothelial Growth Factor A
0
beta Catenin
0
vascular endothelial growth factor A, mouse
0
Tetrodotoxin
4368-28-9
epibatidine
M6K314F1XX
Oxygen
S88TT14065
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2477Subventions
Organisme : NINDS NIH HHS
ID : R01 NS091281
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY026877
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007752
Pays : United States
Organisme : NINDS NIH HHS
ID : P30 NS072031
Pays : United States
Organisme : NEI NIH HHS
ID : K12 EY024225
Pays : United States
Organisme : NEI NIH HHS
ID : K08 EY028999
Pays : United States
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