Microglial depletion decreases Müller cell maturation and inner retinal vascular density

Abstract

The neuroretinal vascular system is comprised of three interconnected layers. The initial superficial vascular plexus formation is guided by astrocytes around birth in mice. The formation of the deep and intermediate vascular plexuses occurs in the second postnatal week and is driven by Muller-cell-derived angiogenic signaling. Previously, we reported that microglia play an important role in regulating astrocyte density during superficial vascular plexus formation. Here, we investigated the role for microglia in regulating Muller-cell-dependent inner retinal vascular development. Results from this study show that microglia closely interact with Muller cells and the growing inner retinal vasculature. Depletion of microglia resulted in reduced inner retinal vascular layers densities and decreased Vegfa isoforms transcript levels. RNA-seq analysis further revealed that microglial depletion significantly reduced specific Muller cell maturation markers including glutamine synthetase, responsible for glutamine biosynthesis, which is needed for angiogenesis. Thus, our study reveals an important role for microglia in Muller cell maturation and inner retinal angiogenesis.