title: Myeloid-Derived Vascular Endothelial Growth Factor and Hypoxia-Inducible Factor Are Dispensable for Ocular Neovascularization--Brief Report.
abstract: OBJECTIVE
  Ocular neovascularization (ONV) is a pathological feature of sight-threatening human diseases, such as diabetic retinopathy and age-related macular degeneration. Macrophage depletion in mouse models of ONV reduces the formation of pathological blood vessels, and myeloid cells are widely considered an important source of the vascular endothelial growth factor A (VEGF). However, the importance of VEGF or its upstream regulators hypoxia-inducible factor-1α (HIF1α) and hypoxia-inducible factor-2α (HIF2α) as myeloid-derived regulators of ONV remains to be determined.
  
  
  RESULTS
  We used 2 mouse models of ONV, choroidal neovascularization and oxygen-induced retinopathy, to show that Vegfa is highly expressed by several cell types, but not myeloid cells during ONV. Moreover, myeloid-specific VEGF ablation did not reduce total ocular VEGF during choroidal neovascularization or oxygen-induced retinopathy. In agreement, the conditional inactivation of Vegfa, Hif1a, or Epas1 in recruited and resident myeloid cells that accumulated at sites of neovascularization did not significantly reduce choroidal neovascularization or oxygen-induced retinopathy.
  
  
  CONCLUSIONS
  The finding that myeloid cells are not a significant local source of VEGF in these rodent models of ONV suggests that myeloid function in neovascular eye disease differs from skin wound healing and other neovascular pathologies.
authors.affiliation: From the Divisions of Genetics (S.E.L., P.V., C.A.L., E.C., A.J.S., R.R.A., U.F.L., J.W.B.) and Cell Biology (A.F., L.D., C.R.), UCL Institute of Ophthalmology, University College London, London, United Kingdom.
authors.forename: Sidath E
authors.initials: SE
authors.lastname: Liyanage
authors.affiliation: From the Divisions of Genetics (S.E.L., P.V., C.A.L., E.C., A.J.S., R.R.A., U.F.L., J.W.B.) and Cell Biology (A.F., L.D., C.R.), UCL Institute of Ophthalmology, University College London, London, United Kingdom.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Fantin
authors.affiliation: From the Divisions of Genetics (S.E.L., P.V., C.A.L., E.C., A.J.S., R.R.A., U.F.L., J.W.B.) and Cell Biology (A.F., L.D., C.R.), UCL Institute of Ophthalmology, University College London, London, United Kingdom.
authors.forename: Pilar
authors.initials: P
authors.lastname: Villacampa
authors.affiliation: From the Divisions of Genetics (S.E.L., P.V., C.A.L., E.C., A.J.S., R.R.A., U.F.L., J.W.B.) and Cell Biology (A.F., L.D., C.R.), UCL Institute of Ophthalmology, University College London, London, United Kingdom.
authors.forename: Clemens A
authors.initials: CA
authors.lastname: Lange
authors.affiliation: From the Divisions of Genetics (S.E.L., P.V., C.A.L., E.C., A.J.S., R.R.A., U.F.L., J.W.B.) and Cell Biology (A.F., L.D., C.R.), UCL Institute of Ophthalmology, University College London, London, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Denti
authors.affiliation: From the Divisions of Genetics (S.E.L., P.V., C.A.L., E.C., A.J.S., R.R.A., U.F.L., J.W.B.) and Cell Biology (A.F., L.D., C.R.), UCL Institute of Ophthalmology, University College London, London, United Kingdom.
authors.forename: Enrico
authors.initials: E
authors.lastname: Cristante
authors.affiliation: From the Divisions of Genetics (S.E.L., P.V., C.A.L., E.C., A.J.S., R.R.A., U.F.L., J.W.B.) and Cell Biology (A.F., L.D., C.R.), UCL Institute of Ophthalmology, University College London, London, United Kingdom.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Smith
authors.affiliation: From the Divisions of Genetics (S.E.L., P.V., C.A.L., E.C., A.J.S., R.R.A., U.F.L., J.W.B.) and Cell Biology (A.F., L.D., C.R.), UCL Institute of Ophthalmology, University College London, London, United Kingdom.
authors.forename: Robin R
authors.initials: RR
authors.lastname: Ali
authors.affiliation: From the Divisions of Genetics (S.E.L., P.V., C.A.L., E.C., A.J.S., R.R.A., U.F.L., J.W.B.) and Cell Biology (A.F., L.D., C.R.), UCL Institute of Ophthalmology, University College London, London, United Kingdom.
authors.forename: Ulrich F
authors.initials: UF
authors.lastname: Luhmann
authors.affiliation: From the Divisions of Genetics (S.E.L., P.V., C.A.L., E.C., A.J.S., R.R.A., U.F.L., J.W.B.) and Cell Biology (A.F., L.D., C.R.), UCL Institute of Ophthalmology, University College London, London, United Kingdom. c.ruhrberg@ucl.ac.uk j.bainbridge@ucl.ac.uk.
authors.forename: James W
authors.initials: JW
authors.lastname: Bainbridge
authors.affiliation: From the Divisions of Genetics (S.E.L., P.V., C.A.L., E.C., A.J.S., R.R.A., U.F.L., J.W.B.) and Cell Biology (A.F., L.D., C.R.), UCL Institute of Ophthalmology, University College London, London, United Kingdom. c.ruhrberg@ucl.ac.uk j.bainbridge@ucl.ac.uk.
authors.forename: Christiana
authors.initials: C
authors.lastname: Ruhrberg
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020256:Choroidal Neovascularization / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000378:metabolism* / Q000473:pathology; D010100:Oxygen; D015861:Retinal Neovascularization / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012171:Retinal Vessels / Q000378:metabolism* / Q000473:pathology; D012178:Retinopathy of Prematurity / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010100:Oxygen; D042461:Vascular Endothelial Growth Factor A; D000099162:Endothelial PAS Domain-Containing Protein 1; C497443:Hif1a protein, mouse; C467480:vascular endothelial growth factor A, mouse
keywords: choroidal neovascularization; diabetic retinopathy; macular degeneration; myeloid cells; vascular endothelial growth factor A