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G.A. Lutty, T. Hasegawa, C. Merges, T. Prow, R. Grebe, D.S. McLeod; The Embryonic Human Hyaloid Vasculature Develops by Hemovasculogenesis . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3876.
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© ARVO (1962-2015); The Authors (2016-present)
The transient hyaloid vasculature in embryonic and fetal human vitreous is responsible for nourishment of the developing lens and avascular retina. The mechanism(s) by which this vasculature forms is unknown.
Eyes from human fetuses ranging in age from 6 to 12 weeks gestation (WG) were either cryopreserved or embedded whole in glycol methacrylate (JB4) for serial sectioning. Immunohistochemistry was performed on serial sections using an alkaline phosphatase system and antibodies against the following antigens: epsilon hemoglobin (E–Hb)(an embryonic hemoglobin only in erythroblasts), CD31, CD34, CD39 (ecto–ADPase), CD 45, VEGF–A, VEGFR–1, VEGFR–2, Ang 1, Ang 2, Tie–2, stem cell factor (SCF), cKit, SDF–1, and CXCR–4. Double labeling was performed with immunofluorescence and confocal microscopy.
Serial JB4 sections from 6 and 7WG eyes stained with Giemsa revealed nucleated RBCs and mesenchymal precursor–like cells in structures that appeared to be blood islands in vitreous. In double labeled cryosections, E–Hb and CD31 or CD34 were present in the nucleated RBCs in blood islands suggesting erythroblasts and endothelial cells shared a common precursor, i.e. the hemangioblast. Some cells in the blood islands were positive for each marker and receptor investigated, as occurs at sites of hematopoiesis. This suggests that both blood vessels (CD31+, CD34+, CD39+, VEGFR–1+, VEGFR–2+, Tie–2+, CXCR–4+) and blood cells (E–Hb+, CD45+) formed from these blood islands as occurs in hemovasculogenesis. SCF, Ang1, and Ang2 were localized to the entire blood island while SDF–1 was diffuse throughout vitreous. VEGF was only present in a small number of cells in the blood islands. After 8 WG, few erythroblasts were observed, the structures in vitreous had formed lumens, and the levels of growth factors declined in the hyaloid vessels.
The human hyaloid vasculature in vitreous forms in the embryo by a unique process, hemovasculogenesis. This in situ formation of blood vessels and blood cells from common precursors in blood island formations has recently been reported in many organ systems in embryonic mouse (Sequira Lopez ML, et al. Am J Physiol Regul Integr Comp Physiol 284:R1126, 2003).
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