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G.A. Lutty, T. Hasegawa, S. McLeod; Fetal Human Retinal Angioblasts Express Early Markers of Hemangioblasts/Endothelial Progenitor Cells . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4754.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: There is increasing evidence that the hemangioblast, a common progenitor for hematopoietic cells and endothelial cells, participates in embryonic and extra–embryonic vasculogenesis in some organs. Whether resident angioblasts or endothelial progenitor cells (EPC's) contribute to human retinal vasculogenesis is still a matter of controversy. Because of the lack of specific markers for angioblasts, this controversy remains unresolved. Methods: Serial cryosections of fetal human retinas of 8–20 weeks gestational age (WG) were examined using immunohistochemistry and a panel of 30 antibodies. We used known endothelial cell markers (CD34, CD31), a marker for actively differentiating retinal angioblasts and endothelium (CD39/ecto–ADPase), markers for astrocyte precursor cells (APC's, Pax–2) and astrocytes (GFAP), markers for microglia (CD45, MHC–II, CD68), growth factor antibodies (VEGF, Ang–1, Ang–2, stromal–derived factor–1 [SDF–1], stem cell factor [SCF] and their receptors (Flk–1, Flt–1, Tie–2, CXCR4, c–kit). Additionally, we used Ki67 to label proliferating cells and double labeling with confocal spectral analysis to identify the proliferating cells associated with vasculogenesis. Results: In the inner neuroblastic layer of the 8WG retina and in the putative ganglion cell layer in avascular regions of older eyes (14WG–20WG), we found some scattered CD39 positive cells (presumed differentiating angioblasts) and numerous progenitor cells (presumed undifferentiated angioblasts) that expressed early markers for EPC's and/or hemangioblasts. These included growth factor receptors Flk–1, Tie–2, CXCR4 and c–kit. VEGF, Ang–2, SDF–1 and SCF immunoreactivity showed a spatial and temporal correlation with the cells expressing the receptors and most appeared associated with nerve fibers. Very few microglia were seen in avascular retina and APC's and astrocytes were only closely associated with formed vasculature. Double labeling and single cell spectral analysis revealed that most proliferating cells at the edge of forming blood vessels were APC's. Conclusions: Angioblasts in fetal human retina express markers in common with hemangioblasts and EPC's from other organs before they differentiate and express endothelial cell antigens. There also appears to be a role for SDF–1/CXCR4 and SCF/c–kit in normal human fetal retinal vasculogenesis.
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