title: Neuropilin-1-Expressing Microglia Are Associated With Nascent Retinal Vasculature Yet Dispensable for Developmental Angiogenesis.
abstract: OBJECTIVE
  Neuropilin-1 (NRP-1) is a transmembrane receptor that is critical for vascular development within the central nervous system (CNS). It binds and influences signaling of several key angiogenic factors, such as VEGF-165, semaphorin 3A, platelet derived growth factor, and more. Neuropilin-1 is expressed by neurons and endothelial cells as well as a subpopulation of proangiogenic macrophages/microglia that are thought to interact with endothelial tip cells to promote vascular anastomosis during brain vascularization. We previously demonstrated a significant role for NRP-1 in macrophage chemotaxis and showed that NRP-1-expressing microglia are major contributors to pathologic retinal angiogenesis. Given this influence on CNS angiogenesis, we now investigated the involvement of microglia-resident NRP-1 in developmental retinal vascularization.
  
  
  METHODS
  We followed NRP-1 expressing microglia during retinal development. We used LysM-cre myeloid lineage-driver cre mice to reduce expression of NRP-1 in retinal myeloid-derived cells and performed a comprehensive morphometric analysis of retinal vasculature during development.
  
  
  RESULTS
  We provide evidence that NRP-1+ microglia are present throughout the retina during vascular development with a preference for the non-vascularized retina. Using LysM-Cre/Nrp1(fl/fl) mice, we reduced NRP-1 expression by ~65% in retinal microglia and demonstrate that deficiency in NRP-1 in these microglia does not impair retinal angiogenesis.
  
  
  CONCLUSIONS
  Our data draw a dichotomous role for NRP-1 in cells of myeloid lineage where it is dispensable for adequate retinal developmental vascularization yet obligate for pathologic retinal angiogenesis.
authors.affiliation: Department of Biochemistry and Molecular Medicine, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada 2Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montrea.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Dejda
authors.affiliation: Department of Biochemistry and Molecular Medicine, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Mawambo
authors.affiliation: Department of Medicine Microbiology, Infectiology and Immunology, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Daudelin
authors.affiliation: Department of Neurology-Neurosurgery, McGill University, Montreal, Quebec, Canada.
authors.forename: Khalil
authors.initials: K
authors.lastname: Miloudi
authors.affiliation: Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Naoufal
authors.initials: N
authors.lastname: Akla
authors.affiliation: Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Chintan
authors.initials: C
authors.lastname: Patel
authors.affiliation: Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Elisabeth M M A
authors.initials: EM
authors.lastname: Andriessen
authors.affiliation: Department of Medicine Microbiology, Infectiology and Immunology, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Labrecque
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Paris, France 6Institut de la Vision, Paris, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Sennlaub
authors.affiliation: Department of Biochemistry and Molecular Medicine, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada 2Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montrea.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Sapieha
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001426:Bacterial Proteins / Q000378:metabolism; D004730:Endothelium, Vascular; D005260:Female; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000502:physiology*; D009024:Morphogenesis / Q000502:physiology; D022423:Myeloid Cells / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D039942:Neuropilin-1 / Q000378:metabolism*; D012171:Retinal Vessels / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; D005456:Fluorescent Dyes; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria; D039942:Neuropilin-1