Microglia refine developing retinal astrocytic and vascular networks through the complement C3/C3aR axis

Gopalan Gnanaguru*, Steven J. Tabor, Gracia M. Bonilla, Ruslan Sadreyev, Kentaro Yuda, Jörg Köhl, Kip M. Connor*

*Korrespondierende/r Autor/-in für diese Arbeit

Abstract

Microglia, a resident immune cell of the central nervous system (CNS), play a pivotal role in facilitating neurovascular development through mechanisms that are not fully understood. Previous reports indicate a role for microglia in regulating astrocyte density. This current work resolves the mechanism through which microglia facilitate astrocyte spatial patterning and superficial vascular bed formation in the neuroretina during development. Ablation of microglia increased astrocyte density and altered spatial patterning. Mechanistically, we show that microglia regulate the formation of the spatially organized astrocyte template required for subsequent vascular growth, through the complement C3/C3aR axis during neuroretinal development. Lack of C3 or C3aR hindered the developmental phagocytic removal of astrocyte bodies and resulted in increased astrocyte density. In addition, increased astrocyte density was associated with elevated proangiogenic extracellular matrix gene expression in C3- and C3aR-deficient retinas, resulting in increased vascular density. These data demonstrate that microglia regulate developmental astrocyte and vascular network spatial patterning in the neuroretina via the complement axis.

OriginalspracheEnglisch
Aufsatznummerdev201047
ZeitschriftDevelopment (Cambridge)
Jahrgang150
Ausgabenummer5
ISSN0950-1991
DOIs
PublikationsstatusVeröffentlicht - 03.2023

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)

DFG-Fachsystematik

  • 204-05 Immunologie

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