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

Author

Listed:
  • G. A. Weiner

    (University of California, San Diego
    University of California, San Diego)

  • S. H. Shah

    (University of California, San Diego
    University of California, San Diego
    Stanford University)

  • C. M. Angelopoulos

    (University of California, San Diego)

  • A. B. Bartakova

    (University of California, San Diego)

  • R. S. Pulido

    (University of California, San Diego)

  • A. Murphy

    (University of California, San Diego)

  • E. Nudleman

    (University of California, San Diego)

  • R. Daneman

    (University of California, San Diego)

  • J. L. Goldberg

    (Stanford University
    University of California, San Diego)

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.

Suggested Citation

  • G. A. Weiner & S. H. Shah & C. M. Angelopoulos & A. B. Bartakova & R. S. Pulido & A. Murphy & E. Nudleman & R. Daneman & J. L. Goldberg, 2019. "Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10219-8
    DOI: 10.1038/s41467-019-10219-8
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    Cited by:

    1. Yonggang Fan & Weixin Zhang & Xiusheng Huang & Mingzhe Fan & Chenhao Shi & Lantian Zhao & Guofu Pi & Huafeng Zhang & Shuangfei Ni, 2024. "Senescent-like macrophages mediate angiogenesis for endplate sclerosis via IL-10 secretion in male mice," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    2. Haifeng Zhang & Busu Li & Qunhua Huang & Francesc López-Giráldez & Yoshiaki Tanaka & Qun Lin & Sameet Mehta & Guilin Wang & Morven Graham & Xinran Liu & In-Hyun Park & Anne Eichmann & Wang Min & Jenny, 2022. "Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas," Nature Communications, Nature, vol. 13(1), pages 1-21, December.

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