Microglia in the Retina: Roles in Development, Maturity, and Disease

Abstract

Microglia, the primary resident immune cell type, constitute a key population of glia in the retina. Recent evidence indicates that microglia play significant functional roles in the retina at different life stages. During development, retinal microglia regulate neuronal survival by exerting trophic influences and influencing programmed cell death. During adulthood, ramified microglia in the plexiform layers interact closely with synapses to maintain synaptic structure and function that underlie the retina's electrophysiological response to light. Under pathological conditions, retinal microglia participate in potentiating neurodegeneration in diseases such as glaucoma, retinitis pigmentosa, and age-related neurodegeneration by producing proinflammatory neurotoxic cytokines and removing living neurons via phagocytosis. Modulation of pathogenic microglial activation states and effector mechanisms has been linked to neuroprotection in animal models of retinal diseases. These findings have led to the design of early proof-of-concept clinical trials with microglial modulation as a therapeutic strategy.

Macrophage Plasticity and Function in the Eye and Heart

“…As in the cardiovascular system and elsewhere, multiple populations of macrophages with distinct origins function in the eye under healthy maintenance or diseased states ( Figure 2). Microglia of the murine central nervous system (CNS) are a long-lived, self-replenishing tissue-resident population of mononuclear phagocytes derived from the yolk sac [34]. Recent lineage tracing in mice has also confirmed the yolk sac origin of retinal microglia [35].…”

Developmental roles of microglia: A window into mechanisms of disease

“…Microglia have also been implicated in retinal neurodegenerative diseases, including age-related macular degeneration (AMD) and glaucoma, which are the leading causes of blindness (Silverman and Wong, 2018). AMD primarily affects photoreceptors along with associated retinal pigmented epithelium (Al-Zamil and Yassin, 2017).…”

Soluble CX3CL1 gene therapy improves cone survival and function in mouse models of retinitis pigmentosa

“…By numerous pathways, DAMPs can then stimulate proinflammatory cytokine activity or recruit immune cells, such as neutrophils and T cells, to the site of cell death (17). Even in homeostatic conditions, the retina is continuously surveyed by microglia, resident macrophages of the central nervous system (CNS) derived from myeloid progenitors in the embryonic yolk sac (19,20). Following injury or exposure to noxious stimuli, microglia may become activated, a state characterized by acquisition of an ameboid morphology, up-regulation of cytokines, and increased phagocytosis of cell debris (21)(22)(23).…”