Microglia versus Monocytes: Distinct Roles in Degenerative Diseases of the Retina

Unlike in the healthy mammalian retina, macrophages in retinal degenerative states are not solely comprised of microglia but may include monocyte-derived recruits. Recent studies have applied transgenics, lineage-tracing, and transcriptomics to help decipher the distinct roles of these two cell types in the disease settings of inherited retinal degenerations and age-related macular degeneration. Literature discussed here focuses on the ectopic presence of both macrophage types in the extracellular site surrounding the outer aspect of photoreceptor cells (i.e., the subretinal space), which is crucially involved in the pathobiology. From these studies we propose a working model in which perturbed photoreceptor states cause microglial dominant migration to the subretinal space as a protective response, whereas the abundant presence of monocyte-derived cells there instead drives and accelerates pathology. The latter, we propose, is underpinned by specific genetic and nongenetic determinants that lead to a maladaptive macrophage state.