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T. Hasegawa, D.S. McLeod, I. Bhutto, T. Prow, C. Merges, R. Grebe, G.A. Lutty; Mechanisms of Embryonic and Fetal Human Choroidal Vascular Development . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2598.
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© ARVO (1962-2015); The Authors (2016-present)
Little is known about normal choroidal vascular development in the embryonic and fetal human eye. Vasculogenesis and/or angiogenesis are conventionally thought to be the principle modes for new vessel formation. Hemovasculogenesis is the formation of endothelial cells accompanied by the simultaneous generation of red blood cells (erythroblasts) in blood islands of the embryo. The purpose of this study is to investigate the mechanism(s) of normal human choroidal vascular development.
Serial cryosections of human choroids of 6–23 weeks gestation (WG) were examined immunohistochemically. Antibodies used were markers of endothelial cells (CD34, CD31), angioblasts and endothelial cells (CD39), erythroblasts [Epsilon Hemoglobin (E–Hb)], hematopoietic cells (CD45, HLA–DR), proliferating cells (Ki67), VEGF–A, and its receptors (VEGFR–1, VEGFR–2). Immunofluorescence was used for double labeling to identify the characteristics of the cell types involved. Additionally, human choroids of 6–12 WG were embedded in JB–4 for Wright’s Giemsa staining.
At 6–7 WG, many erythroblasts (nucleated RBCs by Giemsa staining) were observed in the choriocapillaris layer. Some erythroblasts were separated from and independent of any vascular structure. Many erythroblasts (E–Hb+) were also positive for CD34, CD31 and/or VEGFR–2. Few E–Hb+ cells were positive for Ki67. At this stage, few definitive vascular lumens were detected. VEGF immunoreactivity increased between 6WG and 7WG. By 8–12 WG, most of E–Hb+ cells had disappeared and vascular lumens became apparent. At 14–23 WG, no E–Hb+ cells were seen. Some Ki67 positive cells were also positive for CD34 and/or CD39, especially at the scleral side of choroicapillaris where they were associated with forming deeper choroidal vessels. Immunoreactivity of VEGFR–1 was associated with large choroidal vessels and increased after 14WG.
Choroidal vascular development in the embryo and fetus appears to occur in successive stages. Embryonically, the choriocapillaris appears to initially form by hemovasculogenesis (E–Hb+/CD31+ cells), while angiogenesis appears to be the mode of large choroidal vessel development (CD34+/Ki67+).
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