Anti−Inflammatory Role of Netrin−4 in Diabetic Retinopathy

Diabetic retinopathy is characterized by dysfunction of the retinal vascular network, combined with a persistent low-grade inflammation that leads to vision-threatening complications. Netrin−4 (NTN4) is a laminin-related secreted protein and guidance cue molecule present in the vascular basal membra...

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Main Authors:	Sergio Crespo-Garcia, Nadine Reichhart, Norbert Kociok, Sergej Skosyrski, Antonia M. Joussen
Format:	Article
Language:	English
Published:	MDPI AG 2021-04-01
Series:	International Journal of Molecular Sciences
Subjects:	netrin−4 retina diabetic retinopathy chronic inflammation in vivo
Online Access:	https://www.mdpi.com/1422-0067/22/9/4481

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record_format	Article
spelling	doaj-cb78aaf66915468fb3ddfcc339d1ac292021-04-25T23:03:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01224481448110.3390/ijms22094481Anti−Inflammatory Role of Netrin−4 in Diabetic RetinopathySergio Crespo-Garcia0Nadine Reichhart1Norbert Kociok2Sergej Skosyrski3Antonia M. Joussen4Experimental Ophthalmology, Department of Ophthalmology, Charité—Universitätsmedizin Berlin, Freie Universität, Humboldt-University, The Berlin Institute of Health, Augustenburger Pl. 1, 13353 Berlin, GermanyExperimental Ophthalmology, Department of Ophthalmology, Charité—Universitätsmedizin Berlin, Freie Universität, Humboldt-University, The Berlin Institute of Health, Augustenburger Pl. 1, 13353 Berlin, GermanyExperimental Ophthalmology, Department of Ophthalmology, Charité—Universitätsmedizin Berlin, Freie Universität, Humboldt-University, The Berlin Institute of Health, Augustenburger Pl. 1, 13353 Berlin, GermanyExperimental Ophthalmology, Department of Ophthalmology, Charité—Universitätsmedizin Berlin, Freie Universität, Humboldt-University, The Berlin Institute of Health, Augustenburger Pl. 1, 13353 Berlin, GermanyExperimental Ophthalmology, Department of Ophthalmology, Charité—Universitätsmedizin Berlin, Freie Universität, Humboldt-University, The Berlin Institute of Health, Augustenburger Pl. 1, 13353 Berlin, GermanyDiabetic retinopathy is characterized by dysfunction of the retinal vascular network, combined with a persistent low-grade inflammation that leads to vision-threatening complications. Netrin−4 (NTN4) is a laminin-related secreted protein and guidance cue molecule present in the vascular basal membrane and highly expressed in the retina. A number of studies inferred that the angiogenic abilities of NTN4 could contribute to stabilize vascular networks and modulate inflammation. Analyzing human specimens, we show that <i>NTN4 </i>and netrin receptors are upregulated in the diabetic retina. We further evaluated a knock−out model for NTN4 undergoing experimental diabetes induced by streptozotocin. We investigated retina function and immune cells in vivo and demonstrated that NTN4 provides a protective milieu against inflammation in the diabetic retina and prevents cytokine production.https://www.mdpi.com/1422-0067/22/9/4481netrin−4retinadiabetic retinopathychronic inflammationin vivo
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Sergio Crespo-Garcia Nadine Reichhart Norbert Kociok Sergej Skosyrski Antonia M. Joussen
spellingShingle	Sergio Crespo-Garcia Nadine Reichhart Norbert Kociok Sergej Skosyrski Antonia M. Joussen Anti−Inflammatory Role of Netrin−4 in Diabetic Retinopathy International Journal of Molecular Sciences netrin−4 retina diabetic retinopathy chronic inflammation in vivo
author_facet	Sergio Crespo-Garcia Nadine Reichhart Norbert Kociok Sergej Skosyrski Antonia M. Joussen
author_sort	Sergio Crespo-Garcia
title	Anti−Inflammatory Role of Netrin−4 in Diabetic Retinopathy
title_short	Anti−Inflammatory Role of Netrin−4 in Diabetic Retinopathy
title_full	Anti−Inflammatory Role of Netrin−4 in Diabetic Retinopathy
title_fullStr	Anti−Inflammatory Role of Netrin−4 in Diabetic Retinopathy
title_full_unstemmed	Anti−Inflammatory Role of Netrin−4 in Diabetic Retinopathy
title_sort	anti−inflammatory role of netrin−4 in diabetic retinopathy
publisher	MDPI AG
series	International Journal of Molecular Sciences
issn	1661-6596 1422-0067
publishDate	2021-04-01
description	Diabetic retinopathy is characterized by dysfunction of the retinal vascular network, combined with a persistent low-grade inflammation that leads to vision-threatening complications. Netrin−4 (NTN4) is a laminin-related secreted protein and guidance cue molecule present in the vascular basal membrane and highly expressed in the retina. A number of studies inferred that the angiogenic abilities of NTN4 could contribute to stabilize vascular networks and modulate inflammation. Analyzing human specimens, we show that <i>NTN4 </i>and netrin receptors are upregulated in the diabetic retina. We further evaluated a knock−out model for NTN4 undergoing experimental diabetes induced by streptozotocin. We investigated retina function and immune cells in vivo and demonstrated that NTN4 provides a protective milieu against inflammation in the diabetic retina and prevents cytokine production.
topic	netrin−4 retina diabetic retinopathy chronic inflammation in vivo
url	https://www.mdpi.com/1422-0067/22/9/4481
work_keys_str_mv	AT sergiocrespogarcia antiinflammatoryroleofnetrin4indiabeticretinopathy AT nadinereichhart antiinflammatoryroleofnetrin4indiabeticretinopathy AT norbertkociok antiinflammatoryroleofnetrin4indiabeticretinopathy AT sergejskosyrski antiinflammatoryroleofnetrin4indiabeticretinopathy AT antoniamjoussen antiinflammatoryroleofnetrin4indiabeticretinopathy
_version_	1721509173843197952

Anti−Inflammatory Role of Netrin−4 in Diabetic Retinopathy

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