From blood islands to blood vessels: Morphologic observations and expression of key molecules during hyaloid vascular system development

D. Scott Mcleod, Takuya Hasegawa, Takayuki Baba, Rhonda Grebe, Ines Galtier d'Auriac, Carol Merges, Malia Edwards, Gerard A. Lutty

Research output: Contribution to journalArticlepeer-review


Purpose. 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 immunohistochem-ical analysis or for light and electron microscopy. Immunolab-eling 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-e), 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-e 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 hemato-poiesis occur simultaneously from common precursors, hemangioblasts.

Original languageEnglish (US)
Pages (from-to)7912-7927
Number of pages16
JournalInvestigative Ophthalmology and Visual Science
Issue number13
StatePublished - Dec 2012

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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