Microglia increases the proliferation of retinal precursor cells during postnatal development

Mol Vis. 2018 Jul 30:24:536-545. eCollection 2018.

Abstract

Purpose: In mice, retinal development continues throughout the postnatal stage accompanied by the proliferation of retinal precursor cells. Previous reports showed that during the postnatal stage microglia increase from postnatal day 0 (P0) to P7. However, how microglia are associated with retinal development remains unknown.

Methods: The involvement of microglia in retinal development was investigated by two approaches, microglial activation and loss, using lipopolysaccharide (LPS) and PLX3397 (pexidartinib), respectively.

Results: LPS injection at 1 mg/kg, intraperitoneally (i.p.) in the neonatal mice increased the number of retinal microglia at P7. 5-Bromo-2´-deoxyuridine (BrdU)-positive proliferative cells were increased by LPS treatment compared to the control group. The proliferative cells were mainly colocalized with paired box 6 (Pax6), a marker of retinal precursor cells. However, the depletion of microglia by treatment with PLX3397 decreased the BrdU-positive proliferative cells. Moreover, progranulin deficiency decreased the number of microglia and retinal precursor cells.

Conclusions: These findings indicated that microglia regulate the proliferation of immature retinal cells.

MeSH terms

  • Aminopyridines / pharmacology
  • Animals
  • Animals, Newborn
  • Bromodeoxyuridine
  • Calbindins / genetics
  • Calbindins / metabolism
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Cell Communication / drug effects
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Developmental*
  • Granulins
  • Injections, Intraperitoneal
  • Intercellular Signaling Peptides and Proteins / deficiency
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Microglia / cytology*
  • Microglia / drug effects
  • Microglia / metabolism
  • Nestin / genetics
  • Nestin / metabolism
  • Organogenesis / drug effects
  • Organogenesis / genetics
  • PAX6 Transcription Factor / genetics*
  • PAX6 Transcription Factor / metabolism
  • Progranulins
  • Pyrroles / pharmacology
  • Retina / cytology*
  • Retina / drug effects
  • Retina / metabolism
  • Rhodopsin / genetics
  • Rhodopsin / metabolism
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / metabolism

Substances

  • Aif1 protein, mouse
  • Aminopyridines
  • Calbindins
  • Calcium-Binding Proteins
  • Granulins
  • Grn protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Lipopolysaccharides
  • Microfilament Proteins
  • NES protein, human
  • Nestin
  • PAX6 Transcription Factor
  • Pax6 protein, mouse
  • Progranulins
  • Pyrroles
  • pexidartinib
  • Rhodopsin
  • Bromodeoxyuridine