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The TSPO-NOX1 axis controls phagocyte-triggered pathological angiogenesis in the eye

Author

Listed:
  • Anne Wolf

    (Faculty of Medicine and University Hospital Cologne)

  • Marc Herb

    (Immunology and Hygiene)

  • Michael Schramm

    (Immunology and Hygiene)

  • Thomas Langmann

    (Faculty of Medicine and University Hospital Cologne
    University of Cologne)

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.

Suggested Citation

  • Anne Wolf & Marc Herb & Michael Schramm & Thomas Langmann, 2020. "The TSPO-NOX1 axis controls phagocyte-triggered pathological angiogenesis in the eye," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16400-8
    DOI: 10.1038/s41467-020-16400-8
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