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Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation.

Abstract：

: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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Weiner GA,Shah SH,Angelopoulos CM,Bartakova AB,Pulido RS,Murphy A,Nudleman E,Daneman R,Goldberg JL

doi

10.1038/s41467-019-10219-8

subject

Has Abstract

pub_date

2019-06-06 00:00:00

pages

2477

issue

1

issn

2041-1723

pii

10.1038/s41467-019-10219-8

journal_volume

10

pub_type

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