The human choriocapillaris develops by hemovasculogenesis

Abstract

Vasculogenesis and angiogenesis are the conventional modes for vascular development. Hemovasculogenesis is the formation of endothelial (ECs), hematopoietic, and erythropoietic cells simultaneously from a common precursor, the hemangioblast, as in blood islands. The purpose of this study was to investigate the mechanism(s) of normal human choroidal vascular development. Immunohistochemical analysis of human choroids of 6–23 weeks gestation (WG) was performed with antibodies for markers of ECs (CD34, CD31), angioblasts and ECs (CD39), erythroblasts [Epsilon Hemoglobin (E-Hb)], proliferating cells (Ki67), and VEGFR-2. At 6–7 WG, many erythroblasts (E-Hb+) were observed in the choriocapillaris layer and some were separated from and independent of any vascular structure. Many erythroblasts (E-Hb+) also expressed CD34, CD31 and/or VEGFR-2. At this stage, few definitive vascular lumens were detected. By 9 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 choriocapillaris where they were associated with forming deeper choroidal vessels. Embryonically, the choriocapillaris appears to form by hemovasculogenesis (E-Hb+/CD31+ cells), while angiogenesis appears to be the mode of large choroidal vessel development (CD34+/Ki67+).