Microglial regulation of the retinal vasculature in health and during the pathology associated with diabetes

Abstract

The high metabolic demand of retinal neurons requires a precisely regulated vascular system that can deliver rapid changes in blood flow in response to neural need. In the retina, this is achieved via the action of a coordinated group of cells that form the neurovascular unit. While cells such as pericytes, Müller cells, and astrocytes have long been linked to neurovascular coupling, more recently the resident microglial population have also been implicated. In the healthy retina, microglia make extensive contact with blood vessels, as well as neuronal synapses, and are important in vascular patterning during development. Work in the brain and retina has recently indicated that microglia can directly regulate the local vasculature. In the retina, the fractalkine-Cx3cr1 signalling axis has been shown to induce local capillary constriction within the superficial vascular plexus via a mechanism involving components of the renin-angiotensin system. Furthermore, aberrant microglial induced vasoconstriction may be at the centre of early vascular reactivity changes observed in those with diabetes. This review summarizes the recent emerging evidence that microglia play multiple roles in retinal homeostasis especially in regulating the vasculature. We highlight what is known about the role of microglia under normal circumstances, and then build on this to discuss how microglia contribute to early vascular compromise during diabetes. Further understanding of the mechanisms of microglial-vascular regulation may allow alternate treatment strategies to be devised to reduce vascular pathology in diseases such as diabetic retinopathy.