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- W4384038468 abstract "Interactions among neuronal, glial and vascular components are crucial for retinal angiogenesis and blood-retinal barrier (BRB) maturation. Although synaptic dysfunctions precede 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 and functional validation, we show that deep plexus angiogenesis and paracellular BRB maturation are delayed in Vglut1-/- retinas, where neurons fail to release glutamate. In contrast, deep plexus angiogenesis and paracellular BRB maturation are accelerated in Gnat1-/- retinas, where constitutively depolarized rods release excessive glutamate. Norrin mRNA expression and endothelial Norrin/β-catenin activity are downregulated in Vglut1-/- retinas, and upregulated in Gnat1-/- retinas. Pharmacological activation of endothelial Norrin/β-catenin signaling in Vglut1-/- retinas rescued defects in deep plexus angiogenesis and paracellular BRB integrity. Our findings demonstrate that glutamatergic neuronal activity regulates retinal angiogenesis and BRB maturation by modulating Norrin/β-catenin signaling." @default.
- W4384038468 created "2023-07-13" @default.
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- W4384038468 date "2023-07-11" @default.
- W4384038468 modified "2023-09-30" @default.
- W4384038468 title "Glutamatergic neuronal activity regulates angiogenesis and blood-retinal barrier maturation via Norrin/β-catenin signaling" @default.
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- W4384038468 doi "https://doi.org/10.1101/2023.07.10.548410" @default.
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