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The role of receptor MAS in microglia-driven retinal vascular development

S Foulquier1,2,3, V Caolo4, G Swennen5,6

  • 1Department of Pharmacology-Toxicology, Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands. s.foulquier@maastrichtuniversity.nl.

Angiogenesis
|June 27, 2019
PubMed
Abstract

Insights

The MAS receptor, crucial for microglia function, promotes retinal vascular growth. Its activation is vital for recruiting microglia and supporting new blood vessel development in the eye.

Area of Science:

  • Neuroscience
  • Vascular Biology
  • Immunology

Background:

  • The MAS receptor (encoded by Mas1) is expressed in microglia and linked to anti-inflammatory effects.
  • Microglia play a role in central nervous system processes, including angiogenesis.
  • The study investigates the potential role of the MAS receptor in microglial-mediated angiogenesis.

Purpose of the Study:

  • To determine the role of the MAS receptor in vascular network development.
  • To investigate the impact of MAS receptor deficiency on retinal angiogenesis.
  • To explore the regulation of MAS receptor expression and its downstream effects in microglia under hypoxic conditions.

Main Methods:

  • Comparative analysis of retinal vascularization in wild-type (WT) and Mas1 knockout (Mas1-/-) mice using Isolectin B4 staining.
  • Quantification of vascular front progression, vascular density, junction density, filopodia, vascular loops, and microglial density.
  • Assessment of Mas1 mRNA expression in primary microglia under hypoxic conditions.
  • Evaluation of Notch1, Dll4, and Jag1 gene expression in primary microglia following stimulation with a MAS agonist.

Main Results:

  • Mas1-/- mice exhibited significantly reduced vascular front progression (-24%) and vascular density (-38%) compared to WT mice.
  • A decrease in filopodia, filopodia bursts, and vascular loops was observed in Mas1-/- mice.
  • Microglial density at the vascular front was reduced in Mas1-/- mice (-26%).
  • Hypoxia significantly increased Mas1 mRNA expression in primary microglia (14-fold).
  • MAS agonist stimulation upregulated Notch1 (+57%), Dll4 (+220%), and Jag1 (+137%) expression in primary microglia.

Conclusions:

  • MAS receptor activation is essential for effective microglia recruitment to the developing retinal vasculature.
  • The MAS receptor plays a critical role in promoting vascular growth in the developing retina.
  • These findings highlight the importance of the MAS receptor-microglia axis in angiogenesis.
Keywords:
AngiogenesisAngiotensin receptorsCNSDevelopmental biologyEndotheliumMacrophageRenin angiotensin systemVascular biology

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