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

Chen Yu1, Christophe Roubeix2, Florian Sennlaub2

  • 1Department of Ophthalmology, Duke University, Durham, NC 27710, USA.

Insights

In retinal degenerative diseases, both microglia and monocyte-derived macrophages infiltrate the subretinal space. Microglia offer protection, while excessive monocyte-derived cells accelerate disease progression.

Area of Science:

  • Ophthalmology
  • Immunology
  • Cell Biology

Background:

  • In healthy retinas, macrophages are primarily microglia.
  • Retinal degenerative diseases involve both microglia and monocyte-derived macrophages in the subretinal space.

Purpose of the Study:

  • To differentiate the roles of microglia and monocyte-derived macrophages in retinal degeneration.
  • To propose a model for macrophage involvement in inherited retinal degenerations and age-related macular degeneration.

Main Methods:

  • Review of studies utilizing transgenics, lineage-tracing, and transcriptomics.
  • Focus on macrophage localization in the subretinal space.

Main Results:

  • Microglia migrate to the subretinal space as a protective response to photoreceptor stress.
  • Abundant monocyte-derived macrophages in the subretinal space drive and accelerate retinal pathology.

Conclusions:

  • A proposed model highlights distinct, context-dependent roles for microglia and monocyte-derived macrophages in retinal disease.
  • Maladaptive macrophage states, influenced by genetic and non-genetic factors, contribute to accelerated pathology.