Universität zu Köln

Kinuthia, Urbanus Muthai, Moehle, Christoph, Adams, Ralf H. ORCID: 0000-0003-3031-7677 and Langmann, Thomas ORCID: 0000-0001-6826-529X (2025). Immunomodulation of inflammatory responses preserves retinal integrity in murine models of pericyte-depletion retinopathy. JCI Insight, 10 (15). American Society for Clinical Investigation (ASCI). ISSN 2379-3708

PDF 184465.2-20250801152638-covered-e0fd13ba177f913fd3156f593ead4cfd.pdf Bereitstellung unter der CC-Lizenz: Creative Commons Attribution. Download (7MB)

Abstract

[Artikel-Nr. e184465] The loss of integrity of the blood retina barrier (BRB) is a key pathological hallmark of vision-threatening complications in diabetic retinopathy (DR). Although DR is considered a microvascular disease, mounting evidence from mouse models and patients show that inflammation is closely connected with microvasculopathy. Inflammatory responses during retinal pathophysiology are often orchestrated by microglia, resident innate immune cells of the retina. However, the precise role of microglia activity during DR pathogenesis remains elusive. Here, we used an anti-PDGFRβ antibody and inducible endothelial cell–specific PDGFB-KO during postnatal development of retinal vasculature to reproduce a key feature of DR pathology in mice. In addition, we applied a minocycline therapy to modulate retinal inflammation. Postnatal depletion of pericytes or loss of PDGFB in retinal vessels altered BRB integrity and triggered secretion of angiogenic and inflammatory factors with concomitant microglia reactivity, which was sustained in retinas of adult mice. Microglia reactivity was accompanied by upregulation of disease-associated genes. Notably, minocycline attenuated the cycle of inflammatory responses in young and mature retinas, thereby preserving retinal vascular and structural integrity in mice. Together, our findings suggest that immunomodulation of microglia-driven inflammatory responses preserves retinal vasculature and maintains BRB integrity in 2 different mouse models of human DR

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Kinuthia, Urbanus Muthai UNSPECIFIED UNSPECIFIED UNSPECIFIED Moehle, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Adams, Ralf H. UNSPECIFIED https://orcid.org/0000-0003-3031-7677 UNSPECIFIED Langmann, Thomas UNSPECIFIED https://orcid.org/0000-0001-6826-529X UNSPECIFIED
URN:	urn:nbn:de:hbz:38-798214
Identification Number:	10.1172/jci.insight.184465
Journal or Publication Title:	JCI Insight
Volume:	10
Number:	15
Date:	8 August 2025
Publisher:	American Society for Clinical Investigation (ASCI)
ISSN:	2379-3708
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Augenheilkunde > Klinik und Poliklinik für Allgemeine Augenheilkunde Zentrum für Molekulare Medizin
Subjects:	Medical sciences Medicine
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/79821