Immunity 50, 723–737 (2019)

The density, morphology and marker expression of microglia vary by brain region. In Immunity, Saban and colleagues characterize distinct classes of microglia in the retina at steady state and during degenerative diseases. The authors show that 85% of retinal microglia are yolk-sack derived and long-lived. Microglia in the inner plexiform layer of the retina, but not those in the outer plexiform layer, are dependent on the microglia maintenance factor IL-34. In models of acute or chronic photoreceptor degeneration, microglia from the inner and outer plexiform layers, but not monocyte-derived macrophages, migrate to the subretinal space, where they downregulate genes encoding homeostatic molecules (e.g., Tmem119, Selplg and Cx3cr1) and upregulate genes encoding molecules in the cell-adhesion, lipid-metabolism and antioxidant pathways. IL-34-deficient mice have defects in cone photoreceptor responses at steady state and have increased damage to the retinal pigmented epithelium during photoreceptor degeneration, possibly owing to loss of dead-photoreceptor clearance.