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T. Chan-Ling, L. C. Baxter, R.-A. Sterling, J. Dahlstrom, E. G. Bean, S. Hughes; Distinct Roles of Vasculogenesis and Angiogenesis in Formation of the Human Choroidal and Retinal Vasculature. Invest. Ophthalmol. Vis. Sci. 2007;48(13):6018.
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© ARVO (1962-2015); The Authors (2016-present)
Our earlier work has shown that both vasculogenesis (formation of blood vessels via the prior invasion of vascular precursor cells) & angiogenesis (formation of blood vessels via budding from existing vessels) play a role in formation of human retinal vasculature. Our aim was to determine if both processes also contribute to formation of human choroid.
Human foetal eyes aged 9-40 weeks gestation (WG) were collected according to guidelines set forth in the Declaration of Helsinki. Choroidal & retinal wholemounts & histological sections were examined using antibodies including Vimentin, CD14, CD31, CD34, CD39 (ecto-ADPase), Factor VIII & histochemical stains (H & E). Endothelial proliferation was examined in retinal & choroidal wholemounts by developing a new method of double-labelling with bromo-deoxyuridine (BrdU) & CD34, a marker specific for vascular endothelial cells. A systematic review of published data for evidence of vasculogenesis & angiogenesis during early stages of choroid formation was also undertaken.
Vimentin+ mesenchymal precursor cells were evident in the region of the incipient choroid at 9 WG, and down regulation of Vimentin was evident with maturation. CD14+ vascular precursor cells (VPCs) were evident in the choroidal stroma throughout fetal life. CD39+/CD34+ VPCs were evident within the choroidal stroma from 10 WG, interspersed amongst CD39+ solid vascular chords in the central one-third of the choroid surrounding the optic nerve head. The choroidal vasculature showed no disc to periphery topography of formation. Increase in vascular density via angiogenic budding from existing vessels was evident in the formation of all 3 choroidal layers from optic nerve head to peripheral choroid.
Our observations lead us to suggest that formation of the human choroid takes place via transformation from Vimentin+ mesenchymal precursor cells to CD14+/CD39+/CD34+ vascular precursor cells. Vasculogenesis plays a far greater role in formation of human choroid than previously reported but angiogenesis also contribute to the formation of the human choroid. Angiogenesis is mediated by hypoxia-induced VEGF, whereas vasculogenesis is independent of VEGF. Greater understanding of the cellular processes & molecular cues regulating vasculogenesis are required to provide a rationale for the treatment of choroidal neovascularization observed in ARMD, the leading cause of blindness in the aged population.
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