Universität zu Köln

Wolf, Anne ORCID: 0000-0003-2551-9821, Herb, Marc ORCID: 0000-0002-7533-0288, Schramm, Michael ORCID: 0000-0003-0226-9129 and Langmann, Thomas (2020). The TSPO-NOX1 axis controls phagocyte-triggered pathological angiogenesis in the eye. Nat. Commun., 11 (1). LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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 (18kDa) (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(CreERT2):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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wolf, Anne UNSPECIFIED orcid.org/0000-0003-2551-9821 UNSPECIFIED Herb, Marc UNSPECIFIED orcid.org/0000-0002-7533-0288 UNSPECIFIED Schramm, Michael UNSPECIFIED orcid.org/0000-0003-0226-9129 UNSPECIFIED Langmann, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-331548
DOI:	10.1038/s41467-020-16400-8
Journal or Publication Title:	Nat. Commun.
Volume:	11
Number:	1
Date:	2020
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NADPH OXIDASE 2; BENZODIAZEPINE-RECEPTOR; TRANSLOCATOR PROTEIN; MACULAR DEGENERATION; REACTIVE OXYGEN; MOUSE MODEL; MICROGLIAL ACTIVATION; TSPO LIGAND; REGENERATION; CALCIUM Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33154