The TSPO-NOX1 axis controls phagocyte-triggered pathological angiogenesis in the eye.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32483169.
- Also identified by DOI 10.1038/s41467-020-16400-8 and PMC identifier 7264151.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 Cx3cr1<sup>CreERT2</sup>:TSPO<sup>fl/fl</sup> 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.
Medical subject headings
- NADPH Oxidase 1
- Neovascularization, Pathologic
- Phagocytes
- Receptors, GABA
- Wet Macular Degeneration