biostudies-literatureWang ZNational Eye InstituteKnights Templar Eye FoundationBoston Children’s Hospital Ophthalmology FoundationMass Lions Eye Research Fund Ince73105https://www.ebi.ac.uk/biostudies/studies/S-EPMC9714971biostudies-literatureUnknown11Amino acid (AA) metabolism in vascular endothelium is important for sprouting angiogenesis. SLC38A5 (solute carrier family 38 member 5), an AA transporter, shuttles neutral AAs across cell membrane, including glutamine, which may serve as metabolic fuel for proliferating endothelial cells (ECs) to promote angiogenesis. Here, we found that <i>Slc38a5</i> is highly enriched in normal retinal vascular endothelium, and more specifically, in pathological sprouting neovessels. <i>Slc38a5</i> is suppressed in retinal blood vessels from <i>Lrp5^-/-</i> and <i>Ndp^y/-</i> mice, both genetic models of defective retinal vascular development with Wnt signaling mutations. Additionally, <i>Slc38a5</i> transcription is regulated by Wnt/β-catenin signaling. Genetic deficiency of <i>Slc38a5</i> in mice substantially delays retinal vascular development and suppresses pathological neovascularization in oxygen-induced retinopathy modeling ischemic proliferative retinopathies. Inhibition of <i>SLC38A5</i> in human retinal vascular ECs impairs EC proliferation and angiogenic function, suppresses glutamine uptake, and dampens vascular endothelial growth factor receptor 2. Together these findings suggest that SLC38A5 is a new metabolic regulator of retinal angiogenesis by controlling AA nutrient uptake and homeostasis in ECs.eLifeAmino acid transporter SLC38A5 regulates developmental and pathological retinal angiogenesis.PMC9714971EY028100EY024963EY031765Career Starter GrantLiu CHChen JFu ZTomita YLi WHYemanyi FHuang SMa JXBritton WRBora KCho SSBlomfield AKWang ZfalseAmino acid transporter SLC38A5 regulates developmental and pathological retinal angiogenesis.Amino acid (AA) metabolism in vascular endothelium is important for sprouting angiogenesis. SLC38A5 (solute carrier family 38 member 5), an AA transporter, shuttles neutral AAs across cell membrane, including glutamine, which may serve as metabolic fuel for proliferating endothelial cells (ECs) to promote angiogenesis. Here, we found that <i>Slc38a5</i> is highly enriched in normal retinal vascular endothelium, and more specifically, in pathological sprouting neovessels. <i>Slc38a5</i> is suppressed in retinal blood vessels from <i>Lrp5^-/-</i> and <i>Ndp^y/-</i> mice, both genetic models of defective retinal vascular development with Wnt signaling mutations. Additionally, <i>Slc38a5</i> transcription is regulated by Wnt/β-catenin signaling. Genetic deficiency of <i>Slc38a5</i> in mice substantially delays retinal vascular development and suppresses pathological neovascularization in oxygen-induced retinopathy modeling ischemic proliferative retinopathies. Inhibition of <i>SLC38A5</i> in human retinal vascular ECs impairs EC proliferation and angiogenic function, suppresses glutamine uptake, and dampens vascular endothelial growth factor receptor 2. Together these findings suggest that SLC38A5 is a new metabolic regulator of retinal angiogenesis by controlling AA nutrient uptake and homeostasis in ECs.2022-01-01T00:00:00Z2022 Dec2025-04-26T12:30:28.808Z2025-04-06T14:00:58.068ZS-EPMC97149713645421410.7554/eLife.73105