title: From blood islands to blood vessels: morphologic observations and expression of key molecules during hyaloid vascular system development.
abstract: OBJECTIVE
  The mode of development of the human hyaloid vascular system (HVS) remains unclear. Early studies suggested that these blood vessels formed by vasculogenesis, while the current concept seems to favor angiogenesis as the mode of development. We examined embryonic and fetal human HVS using a variety of techniques to gain new insights into formation of this vasculature.
  
  
  METHODS
  Embryonic and fetal human eyes from 5.5 to 12 weeks gestation (WG) were prepared for immunohistochemical analysis or for light and electron microscopy. Immunolabeling of sections with a panel of antibodies directed at growth factors, transcription factors, and hematopoietic stem cell markers was employed.
  
  
  RESULTS
  Light microscopic examination revealed free blood islands (BI) in the embryonic vitreous cavity (5.5-7 WG). Giemsa stain revealed that BI were aggregates of mesenchymal cells and primitive nucleated erythroblasts. Free cells were also observed. Immunolabeling demonstrated that BI were composed of mesenchymal cells that expressed hemangioblast markers (CD31, CD34, C-kit, CXCR4, Runx1, and VEGFR2), erythroblasts that expressed embryonic hemoglobin (Hb-ε), and cells that expressed both. Few cells were proliferating as determined by lack of Ki67 antigen. As development progressed (12 WG), blood vessels became more mature structurally with pericyte investment and basement membrane formation. Concomitantly, Hb-ε and CXCR4 expression was down-regulated and von Willebrand factor expression was increased with the formation of Weibel-Palade bodies.
  
  
  CONCLUSIONS
  Our results support the view that the human HVS, like the choriocapillaris, develops by hemo-vasculogenesis, the process by which vasculogenesis, erythropoiesis, and hematopoiesis occur simultaneously from common precursors, hemangioblasts.
authors.affiliation: Wilmer Eye Institute, Baltimore, Maryland 21784, USA.
authors.forename: D Scott
authors.initials: DS
authors.lastname: McLeod
authors.forename: Takuya
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Baba
authors.forename: Rhonda
authors.initials: R
authors.lastname: Grebe
authors.forename: Ines
authors.initials: I
authors.lastname: Galtier d'Auriac
authors.forename: Carol
authors.initials: C
authors.lastname: Merges
authors.forename: Malia
authors.initials: M
authors.lastname: Edwards
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Lutty
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D004900:Erythroblasts / Q000378:metabolism / Q000648:ultrastructure; D005319:Fetal Hemoglobin; D019084:Fluorescent Antibody Technique, Indirect; D005865:Gestational Age; D006801:Humans; D007124:Immunoenzyme Techniques; D007908:Lens, Crystalline / Q000098:blood supply* / Q000196:embryology; D008648:Mesoderm / Q000378:metabolism / Q000648:ultrastructure; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009880:Ophthalmic Artery / Q000196:embryology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014822:Vitreous Body / Q000098:blood supply / Q000196:embryology
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; C527276:CXCR4 protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019718:Receptors, CXCR4; D005319:Fetal Hemoglobin; D019009:Proto-Oncogene Proteins c-kit; D040301:Vascular Endothelial Growth Factor Receptor-2