Friend or Foe? Resident Microglia vs Bone Marrow-Derived Microglia and Their Roles in the Retinal Degeneration

Abstract

Microglia are immune cells in the central nervous system (CNS) that originate from the yolk sac in an embryo. The renewal of the microglia pool in the adult eye consists of two components. In addition to the self-proliferation of resident cells, microglia in the CNS also derive from the bone marrow (BM). BM-derived cells pass through the blood-brain barrier (BBB) or blood-retina barrier (BRB) and differentiate into microglia under specific conditions which involves a complex mechanism. Recent studies have widely investigated the role of resident microglia and BM-derived microglia in the retinal degenerative disease. Both two cell types play dual roles and share many similar functions. However, resident microglia tend to polarize to the M1 phenotype which is pro-inflammatory and neurotoxic, whereas BM-derived microglia mainly polarize to the neuroprotective M2 phenotype in retinal degeneration. The molecular mechanism that underlines the invasion of peripheral cells has led to extensive discussions. In addition to the BBB and BRB disruption, many signaling pathways are involved in this process. Based on these studies, we discuss the roles of these two types of microglia in retinal degeneration disease and the potential clinical application of BM-derived microglia, which may benefit future therapies.

Monocyte infiltration rather than microglia proliferation dominates the early immune response to rapid photoreceptor degeneration

“…During neurodegeneration, local changes in chemokines, purines, and the ionic milieu cause microglia to lose their ramifications and become amoeboid, a cellular state capable of rapid migration and greater phagocytic capacity [7]. Bone marrow-derived monocytes can also be recruited from the systemic circulation to further escalate the inflammatory response, often when the microglia population becomes depleted ( [8] for review). Because infiltrating monocytes differentiate into macrophages that become difficult to distinguish from resident immune cells [9], determining the roles of these populations in the progression of degeneration has been difficult.…”

Microglial‐induced Müller cell gliosis is attenuated by progesterone in a mouse model of retinitis pigmentosa

“…The role of inflammation in degeneration and neuroprotection is a current focus in retinal research (Jin, Gao, Fan, & Xu, ; Karlstetter et al, ; Li, Eter, & Heiduschka, ; Ma & Wong, ; Madeira, Boia, Santos, Ambrosio, & Santiago, ; Ramirez et al, ; Vecino, Rodriguez, Ruzafa, Pereiro, & Sharma, ). Microglia, the resident macrophages of the retina, appear to play a detrimental role in driving degeneration of photoreceptors and exacerbating disease progression (Roche, Wyse‐Jackson, Gomez‐Vicente, et al, 2016; Zhao et al, ).…”

Curcumin Delays Retinal Degeneration by Regulating Microglia Activation in the Retina of rd1 Mice

“…Microglia cells, the first responders to cell damage within the retina, are involved in injury repair and inflammatory state [49]. Typically, activated microglia have two sources from which to play their respective roles: resident microglia tend of the M1 type mainly function in proinflammation and neurotoxin, whereas infiltrated bone marrow (BM)-derived monocytes tend to be of the M2 type with the main function of neuroprotection [3]. In the pathology of RP, the infiltration of BM-derived monocytes is restricted by the physiologic blood-retinal barrier (BRB), which causes neuroprotective function loss in the BM-derived monocytes, and may be the reason the damage in RP worsens rather than being repaired [3, 50].…”

“…Typically, activated microglia have two sources from which to play their respective roles: resident microglia tend of the M1 type mainly function in proinflammation and neurotoxin, whereas infiltrated bone marrow (BM)-derived monocytes tend to be of the M2 type with the main function of neuroprotection [3]. In the pathology of RP, the infiltration of BM-derived monocytes is restricted by the physiologic blood-retinal barrier (BRB), which causes neuroprotective function loss in the BM-derived monocytes, and may be the reason the damage in RP worsens rather than being repaired [3, 50]. CCL2, also called monocyte chemotactic protein 1, is usually secreted by microglia, nerve cells, and astrocytes, and bonds with the surface receptor CCR2 of inflammatory cells.…”

“…These activated microglia, known as amoeboid microglia, migrate from the inner to outer retina and phagocytose the debris of degenerated photoreceptors. Activated microglia also produce pro-inflammatory cytokines, which increase the levels of extracellular reactive oxygen species, resulting in neurotoxicity to photoreceptors and other neurons in the retina [3]. It was shown that the tetracycline antibiotic minocycline could suppress microglial activation by decreasing the apoptosis of photoreceptors in the degenerated retina [5].…”