The Contribution of Microglia to the Development and Maturation of the Visual System

Abstract

Microglia, the resident immune cells of the central nervous system (CNS), were once considered quiescent cells that sat in readiness for reacting to disease and injury. Over the last decade, however, it has become clear that microglia play essential roles in maintaining the normal nervous system. The retina is an easily accessible part of the central nervous system and therefore much has been learned about the function of microglia from studies in the retina and visual system. Anatomically, microglia have processes that contact all synapses within the retina, as well as blood vessels in the major vascular plexuses. Microglia contribute to development of the visual system by contributing to neurogenesis, maturation of cone photoreceptors, as well as refining synaptic contacts. They can respond to neural signals and in turn release a range of cytokines and neurotrophic factors that have downstream consequences on neural function. Moreover, in light of their extensive contact with blood vessels, they are also essential for regulation of vascular development and integrity. This review article summarizes what we have learned about the role of microglia in maintaining the normal visual system and how this has helped in understanding their role in the central nervous system more broadly.

Microglia modulate blood flow, neurovascular coupling, and hypoperfusion via purinergic actions

“…Microglia–vascular interactions are present in the brain from early development into adulthood, through which microglia regulate blood–brain barrier (BBB) permeability, leukocyte extravasation, and angiogenesis ( Dudvarski Stankovic et al, 2016 ; Jolivel et al, 2015 ; Lou et al, 2016 ). In fact, microglia and microglial processes are closely associated with developing blood vessels in the neuroepithelium or in the ventricular zone, while Pu.1 −/− mice or Csf1 op/op mice that lack microglia and macrophages display impaired angiogenesis in the retina ( Arnold and Betsholtz, 2013 ; Dixon et al, 2021 ; Dudvarski Stankovic et al, 2016 ; Penna et al, 2021 ). In the adult brain, CD206-positive perivascular macrophages (PVMs) remain closely associated with blood vessels, while CD206-negative microglial cell bodies occupy the brain parenchyma isolated by the glia limitans ( Goldmann et al, 2016 ; Kida et al, 1993 ; Ransohoff and Engelhardt, 2012 ).…”

Glia Regulate the Development, Function, and Plasticity of the Visual System From Retina to Cortex

“…In the visual cortex astrocytes are not the only glial cell type that has been shown to respond to visual activity and influence circuit development and function. Microglia are also appreciated to contribute to the function of the visual system in important ways (for a dedicated review on microglia and the development of the visual system see Dixon et al, 2021). Here we have included some of the relevant contributions of microglia to the development and function of the visual cortex.…”

cGMP Signaling in the Neurovascular Unit—Implications for Retinal Ganglion Cell Survival in Glaucoma

“…In humans, regarding glial cells, the fovea contains only MG subtypes, indicating that these cells alone are sufficient to supply the metabolic needs of the RGCs [ 13 , 71 ]. Microglia are also resident glial cells that span multiple layers of the retina, yet their exact role in the basal NVU function of the retina is less understood compared to other glial cell types [ 72 ]. Recently, it has been shown in the brain that microglia directly and dynamically contact endothelial, smooth muscle cells, pericytes, and astrocytes, and are able to regulate cerebral blood flow via vasoactive agents, including NO and cGMP [ 73 ].…”