title: Potential role of microglia in retinal blood vessel formation.
abstract: OBJECTIVE
  The role of microglia, present in the retina early in development before vascularization, remains ill defined. The authors investigated whether microglia are implicated in retinal blood vessel formation.
  
  
  METHODS
  The microglia and vasculature of developing human fetal and rodent retinas were examined by labeling the endothelial cells with lectin and the microglia with CD18 antibody or green fluorescent protein driven by the promoter of the chemokine receptor CX(3)CR1. Rodent ischemic proliferative retinopathy induced by hyperoxia or hypercapnia, which model retinopathy of prematurity, and ex vivo retinal explants were used to assess microglial involvement in vascular pathology. Microglial participation in developmental retinal vessel formation was further studied in neonatal rats after pharmacologic macrophage depletion with the use of clodronate liposomes and subsequent intravitreal injection of microglia.
  
  
  RESULTS
  Microglia intimately appose developing vessels of human and murine retinas. Ischemic retinopathy models exhibit decreased microglia concomitant with the characteristic reductions in vasculature observed in these retinopathies. Retinal explants exposed to conditions resulting in ischemic retinopathies (in vivo) reveal that antioxidants protect against microglial loss. Depletion of resident retinal microglia, but not systemic macrophages, reduced developmental vessel growth and density, which were restored by intravitreal microglial injection.
  
  
  CONCLUSIONS
  These observations suggest that proper retinal blood vessel formation requires an adequate resident microglial population because diminished microglia are associated with decreased vascularity in models of ischemic retinopathy and retinal vascular development. In light of these findings, the traditional definition of microglia as merely immunocompetent cells should be reconsidered to encompass this new function related to blood vessel formation.
authors.affiliation: Department of Pediatrics, Research Center, Hôpital Ste. Justine, Montreal, Quebec, Canada.
authors.forename: Daniella
authors.initials: D
authors.lastname: Checchin
authors.forename: Florian
authors.initials: F
authors.lastname: Sennlaub
authors.forename: Etienne
authors.initials: E
authors.lastname: Levavasseur
authors.forename: Martin
authors.initials: M
authors.lastname: Leduc
authors.forename: Sylvain
authors.initials: S
authors.lastname: Chemtob
mesh_terms: D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D004002:Clodronic Acid / Q000008:administration & dosage; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D006935:Hypercapnia / Q000503:physiopathology; D018496:Hyperoxia / Q000503:physiopathology; D007231:Infant, Newborn; D008081:Liposomes; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000502:physiology*; D009024:Morphogenesis / Q000502:physiology*; D010100:Oxygen / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D019707:Receptors, Chemokine / Q000378:metabolism; D012160:Retina / Q000166:cytology*; D012171:Retinal Vessels / Q000196:embryology* / Q000378:metabolism; D012178:Retinopathy of Prematurity / Q000503:physiopathology*
chemical_list: D018821:CD18 Antigens; D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D008081:Liposomes; D019707:Receptors, Chemokine; D004002:Clodronic Acid; D049452:Green Fluorescent Proteins; D010100:Oxygen