Universität zu Köln

Klee, Katrin, Storti, Federica, Barben, Maya, Samardzija, Marijana, Langmann, Thomas, Dunaief, Joshua and Grimm, Christian ORCID: 0000-0001-9318-4352 (2019). Systemic knockout of Tspo in mice does not affect retinal morphology, function and susceptibility to degeneration. Exp. Eye Res., 188. LONDON: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. ISSN 1096-0007

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Abstract

Translocator protein (18 kDa) (TSPO) is a mitochondrial protein expressed by reactive microglia and astrocytes at the site of neuronal injury. Although TSPO function has not been fully determined, synthetic TSPO ligands have beneficial effects on different pathologies of the central nervous system, including the retina. Here, we studied the pattern of Tspo expression in the aging human retina and in two mouse models of retinal degeneration. Using a newly generated Tspo-KO mouse, we investigated the impact of the lack of TSPO on retinal morphology, function and susceptibility to degeneration. We show that TSPO was expressed in both human and mouse retina and retinal pigment epithelium (RPE). Tspo was induced in the mouse retina upon degeneration, but constitutively expressed in the RPE. Similarly, TSPO expression levels in healthy human retina and RPE were not differentially regulated during aging. Tspo , KO mice had normal retinal morphology and function up to 48 weeks of age. Photoreceptor loss caused either by exposure to excessive light levels or by a mutation in the phosphodiesterase 6b gene was not affected by the absence of Tspo. The reactivity states of retinal mononuclear phagocytes following light-damage were comparable in Tspo-KO and control mice. Our data suggest that lack of endogenous TSPO does not directly influence the magnitude of photoreceptor degeneration or microglia activation in these two models of retinal degeneration. We therefore hypothesize that the interaction of TSPO with its ligands may be required to modulate disease progression.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Klee, Katrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Storti, Federica UNSPECIFIED UNSPECIFIED UNSPECIFIED Barben, Maya UNSPECIFIED UNSPECIFIED UNSPECIFIED Samardzija, Marijana UNSPECIFIED UNSPECIFIED UNSPECIFIED Langmann, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Dunaief, Joshua UNSPECIFIED UNSPECIFIED UNSPECIFIED Grimm, Christian UNSPECIFIED orcid.org/0000-0001-9318-4352 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-129414
DOI:	10.1016/j.exer.2019.107816
Journal or Publication Title:	Exp. Eye Res.
Volume:	188
Date:	2019
Publisher:	ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Place of Publication:	LONDON
ISSN:	1096-0007
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PERMEABILITY TRANSITION PORE; TRANSLOCATOR PROTEIN TSPO; BENZODIAZEPINE-RECEPTOR; 18 KDA; MOUSE MODEL; MICROGLIA; ACTIVATION; TARGET; LOCALIZATION; INDUCTION Multiple languages Ophthalmology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12941