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N. Yoshida, N. Katai, A. Sato, N. Yoshimura; Multistep process of retinal neovascularization . Invest. Ophthalmol. Vis. Sci. 2004;45(13):495.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To characterize the developmental process of retinal neovascularization using oxygen–induced retinopathy mice model. Methods: To develop the retinal neovascularization, postnatal day 7 (P7) C57BL/6J mice were exposed to 75% oxygen for 5 days and then returned to room air. The cross–sections and flat–mounted retinas were prepared on P13, P14, P15 and P17 to examine morphological changes of neovascular tissues. Immunohistological examination was perfomed using anti–CD34 and anti–s–100 antibodies. To investigate possible participation of hematopoietic stem cells in retinal neovascularization, we used DiI–labeled hematopoietic stem cells isolated from adult mice bone marrow and injected these cells intravenously into model mice on P12. On P13, P15 and P17, flat–mounted retinas were examined by confocal microscopy after perfused through the left ventricle with FITC–dextran. Results: On P13 of model mice, both vascular endothelial cells and DiI–labeled cells migrated into ischemic area of the retinas. Astrocytes surrounded the cluster of endothelial cells to form the glomerular tufts. Labeled cells were located in glomerular tufts on P14 and P15. There were glomerular tufts with or without blood supply. DiI–labeled cells were also seen in neovascular vessels that extended through the inner limited membrane. Conclusions: The retinal neovascularization may develop through a multistep process, including (1) transendothelial extravasation of endothelial progenitor cells into the interstitial space, (2) encircling by astrocytes, (3) extravascular formation of glomerular tufts, (4) supply of the blood flow to glomerular tufts, (5) breaking through the internal limiting membrane.
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