血管生成
谷氨酸的
细胞生物学
生物
视网膜
神经科学
Wnt信号通路
视网膜
血-视网膜屏障
信号转导
谷氨酸受体
癌症研究
内分泌学
生物化学
受体
糖尿病
糖尿病性视网膜病变
作者
Saptarshi Biswas,Sanjid Shahriar,Galina Bachay,Panos Arvanitis,Danny Jamoul,William J. Brunken,Dritan Agalliu
出处
期刊:Neuron
[Elsevier]
日期:2024-04-01
标识
DOI:10.1016/j.neuron.2024.03.011
摘要
Interactions among neuronal, glial, and vascular components are crucial for retinal angiogenesis and blood-retinal barrier (BRB) maturation. Although synaptic dysfunction precedes vascular abnormalities in many retinal pathologies, how neuronal activity, specifically glutamatergic activity, regulates retinal angiogenesis and BRB maturation remains unclear. Using in vivo genetic studies in mice, single-cell RNA sequencing (scRNA-seq), and functional validation, we show that deep plexus angiogenesis and paracellular BRB maturation are delayed in Vglut1-/- retinas where neurons fail to release glutamate. By contrast, deep plexus angiogenesis and paracellular BRB maturation are accelerated in Gnat1-/- retinas, where constitutively depolarized rods release excessive glutamate. Norrin expression and endothelial Norrin/β-catenin signaling are downregulated in Vglut1-/- retinas and upregulated in Gnat1-/- retinas. Pharmacological activation of endothelial Norrin/β-catenin signaling in Vglut1-/- retinas rescues defects in deep plexus angiogenesis and paracellular BRB maturation. Our findings demonstrate that glutamatergic neuronal activity regulates retinal angiogenesis and BRB maturation by modulating endothelial Norrin/β-catenin signaling.
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