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N. Unoki, T. Murakami, K. Nishijima, N. Yoshimura; Stromal Derived Factor -1 (SDF-1)/CXCR4 Axis Contributes to the Neovascular Sprouting in Retinal Angiogenesis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):527. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Stromal cell-derived factor-1 (SDF-1) was reported to have significant functions in retinal angiogenesis and the recruitment of hematopoietic stem cell-derived cells. We here assessed the contribution of the SDF-1/CXCR4 axis to the neovascular sprouting from the retinal vasculature in ex vivo and in vivo models.
(ex vivo) The retinas isolated from 7- to 8-week-old C57BL6/J mice were cultured for 4 days with 25 ng/ml vascular endothelial growth factor (VEGF), with or without anti-SDF-1 antibody or CXCR4 inhibitor (AMD 3100). The neovascular sprouts (PECAM-positive and collagen type IV negative sprouts) were quantified. For the time-sequential imaging, the retinas of Tie2-GFP transgenic mice were treated with VEGF for 4 days, followed by AMD 3100 treatment and the image acquisition. (in vivo) AMD3100 was intraperitoneally injected into C57BL6/J mice on postnatal day 3 (P3), and the eyes were isolated and fixed on P4. After the staining with anti-PECAM antibodies, the radius of vascular plexus was evaluated by measuring the length between the center of the optic nerve and the edge of leading vessels.
(ex vivo) The treatment with anti-SDF-1 antibody significantly decreased the neovascular sprouts which were induced by VEGF, in the dose dependent manner (control: 82.6±27.8 vs anti-SDF-1 300, 30, 3 µg/ml: 30.7±19.7*, 41.3±12.7*, 52.4±11.2**; *p<0.01, ** p<0.05). Similarly, the neovascular sprouts in the retinas treated with AMD 3100 were significantly attenuated (control: 81.2±20.6 vs AMD3100 30, 3, 0.3µM: 23.2±9.3*, 55.0±6.5**, 53.7±9.7**). Time-lapse imaging demonstrated that AMD 3100 reduced the elongation of each sprout compared to the control, although the leading edges were extended and retracted repeatedly.(in vivo) Systemic administration of AMD 3100 led to the decrease in the radius of vascular plexus (p<0.05). In addition, immunostaining showed that the filopodial extension in the endothelial tip cells was disturbed in the retina with AMD 3100 treatment.
These data indicate that SDF-1/CXCR4 axis may promote the neovascular sprouting from the retinal vasculature.
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