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T. Chan–Ling, L.C. Baxter, J. Dahlstrom, E. Rosinova, E. Bean, S. Hughes; Role of Vasculogenesis and Angiogenesis in the Formation of Human Choroid and Retina . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4756.
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Purpose: Both vasculogenesis (formation of blood vessels via the prior invasion of vascular precursor cells) and angiogenesis (formation of blood vessels via budding from existing vessels) play a role in the formation of the human CNS and retinal vasculature. Our aim was to determine the role of vasculogenesis and angiogenesis in the formation of the human choroid. Methods: Human foetal eyes aged 12 to 20 weeks gestation (WG) were collected. The role of vasculogenesis was examined using histological sections of the fetal eye stained with various antibodies (Vimentin, S–100 (a & b), CD31, CD34, CD39, Factor VIII) and histochemical stains (H & E and Mason trichrome). Angiogenesis was examined using double–label immunohistochemistry (IHC) of retinal and choroidal wholemounts using bromo–deoxyuridine (BrdU) to identify proliferating cells and CD34, a marker specific for vascular endothelial cells. A systematic review of published data for evidence of vasculogenesis during early stages of choroid formation was undertaken. Results: Examination of early published specimens and Vimentin IHC suggest the presence of mesenchymal precursor cells in the region of the incipient choroid. At 12.5 WG, CD34+/CD31+ choriocapillaris was evident from the optic nerve head to ciliary margins. Increase in vascular density via angiogenic budding from existing vessels was evident with combined BrdU/CD34 IHC. Large numbers of BrdU+ vascular endothelial cells were evident throughout the choriocapillaris, medium and large vessel layers. Large numbers of proliferating CD34– stromal cells were also evident. Morphological evidence was consistent with intersusseptive growth as the mechanism of formation of the choriocapillaris. Further, the topography of formation of the choroidal vasculature is distinct from that of the human retinal vasculature. Conclusions: Our observations plus literature analysis lead us to suggest that like the human retina, the choroidal vasculature is formed via a combination of vasculogenesis and angiogenesis but display a distinct topography of formation. These processes are regulated via distinct molecular cues and further understanding of the role of these distinct processes are required if we are to provide a rational for the treatment or prevention of choroidal neovascularization observed in age–related maculopathy, the leading cause of blindness in the aged population.
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