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

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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.

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Abbreviations

Aβ:

Amyloid β

AD:

Alzheimer’s disease

AMD:

Age-related macular degeneration

BBB:

Blood–brain barrier

BCECs:

Brain capillary endothelial cells

BM:

Bone marrow

BRB:

Blood–retina barrier

CNS:

Central nervous system

CNV:

Choroidal neovascularization

DR:

Diabetic retinopathy

EMP:

Erythromyeloid precursors

GCL:

Ganglion cell layer

HIF1α:

Hypoxia inducible factor 1 alpha

HSC:

Hematopoietic stem cells

IGF-1:

Insulin-like growth factor-1

IPL:

Inner plexiform layer

MCP:

Monocyte chemoattractant protein

MHC:

Major histocompatibility complex

MIP:

Macrophage inflammatory protein

MMP:

Matrix metalloproteinases

NFL:

Nerve fiber layer

NV:

Neovascularization

ONL:

Outer nuclear layer

OPL:

Outer plexiform layer

RD:

Retinal degeneration

ROS:

Reactive oxygen species

RP:

Retinitis pigmentosa

RPE:

Retinal pigment epithelium

SDF-1:

Stromal-derived factor-1

VEGF:

Vascular endothelial growth factor

YS:

Yolk sac

7KCh:

7-Ketocholesterol

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Acknowledgments

This work was supported by the National Basic Research Program of China (973 Program, 2013CB967002) and partially supported by the National Nature Science Foundation of China (No. 81570890).

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Authors and Affiliations

  1. Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China

    Ni Jin, Lixiong Gao & Haiwei Xu

  2. Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 400038, China

    Ni Jin, Lixiong Gao & Haiwei Xu

  3. School of Nursing, Third Military Medical University, Chongqing, 400038, China

    Ni Jin

  4. Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, 400038, China

    Xiaotang Fan

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Correspondence to Haiwei Xu.

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Jin, N., Gao, L., Fan, X. et al. Friend or Foe? Resident Microglia vs Bone Marrow-Derived Microglia and Their Roles in the Retinal Degeneration. Mol Neurobiol 54, 4094–4112 (2017). https://doi.org/10.1007/s12035-016-9960-9

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