{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["11(1)"],"submitter":["Wolf A"],"pubmed_abstract":["Aberrant immune responses including reactive phagocytes are implicated in the etiology of age-related macular degeneration (AMD), a major cause of blindness in the elderly. The translocator protein (18?kDa) (TSPO) is described as a biomarker for reactive gliosis, but its biological functions in retinal diseases remain elusive. Here, we report that tamoxifen-induced conditional deletion of TSPO in resident microglia using Cx3cr1CreERT2:TSPOfl/fl mice or targeting the protein with the synthetic ligand XBD173 prevents reactivity of phagocytes in the laser-induced mouse model of neovascular AMD. Concomitantly, the subsequent neoangiogenesis and vascular leakage are prevented by TSPO knockout or XBD173 treatment. Using different NADPH oxidase-deficient mice, we show that TSPO is a key regulator of NOX1-dependent neurotoxic ROS production in the retina. These data define a distinct role for TSPO in retinal phagocyte reactivity and highlight the protein as a drug target for immunomodulatory and antioxidant therapies for AMD."],"journal":["Nature communications"],"pagination":["2709"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7264151"],"repository":["biostudies-literature"],"pubmed_title":["The TSPO-NOX1 axis controls phagocyte-triggered pathological angiogenesis in the eye."],"pmcid":["PMC7264151"],"pubmed_authors":["Wolf A","Schramm M","Herb M","Langmann T"],"additional_accession":[]},"is_claimable":false,"name":"The TSPO-NOX1 axis controls phagocyte-triggered pathological angiogenesis in the eye.","description":"Aberrant immune responses including reactive phagocytes are implicated in the etiology of age-related macular degeneration (AMD), a major cause of blindness in the elderly. The translocator protein (18?kDa) (TSPO) is described as a biomarker for reactive gliosis, but its biological functions in retinal diseases remain elusive. Here, we report that tamoxifen-induced conditional deletion of TSPO in resident microglia using Cx3cr1CreERT2:TSPOfl/fl mice or targeting the protein with the synthetic ligand XBD173 prevents reactivity of phagocytes in the laser-induced mouse model of neovascular AMD. Concomitantly, the subsequent neoangiogenesis and vascular leakage are prevented by TSPO knockout or XBD173 treatment. Using different NADPH oxidase-deficient mice, we show that TSPO is a key regulator of NOX1-dependent neurotoxic ROS production in the retina. These data define a distinct role for TSPO in retinal phagocyte reactivity and highlight the protein as a drug target for immunomodulatory and antioxidant therapies for AMD.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Jun","modification":"2021-02-20T13:15:11Z","creation":"2020-06-16T07:18:23Z"},"accession":"S-EPMC7264151","cross_references":{"pubmed":["32483169"],"doi":["10.1038/s41467-020-16400-8"]}}