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J. Shen, J. Zimmer, Y. Oshima, D. Leahy, P. Campochiaro; Soluble Neuropilin-1 Inhibits Retinal Neovascularization (NV) . Invest. Ophthalmol. Vis. Sci. 2003;44(13):576.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Neuropilin-1 (Npn1) is a coreceptor for vascular endothelial growth factor 165 isoform (VEGF165), which enhances VEGF165 binding to high affinity VEGF receptor 2, and plays an important role in regulation of the mitogenic and chemotactic activity of VEGF. Npn1 plays an important role in vascular development. The aim of this study was to determine whether intraocular injection of a portion of the extracellular domain containing the B1 VEGF binding site, soluble Npn1 (sNpn1), inhibits retinal neovascularization in mice with oxygen-induced ischemic retinopathy. Methods: A protein encompassing the a1, a2, b1, and b2 domains of rat Npn1 was expressed in CHO cells and purified from conditioned medium. Litters of C57BL/6 mice were placed in 75% oxygen at postnatal day P7. At P12, they were removed from oxygen and given an intravitreous injection of 400ng or 800ng of sNpn1 in one eye and in the contralateral eye, they received an injection of 800ng of BSA. At P17, mice were sacrificed and retinal NV was measured by image analysis. At various time points in mice with ischemic retinopathy that were not injected with sNpn1, Npn1 mRNA levels in the retina were assessed by RT-PCR and Npn1 expression was localized by immunohistochemistry. Results: In mice with ischemic retinopathy, increased levels of Npn1 mRNA were present in the retina from P13 to p17. Staining for Npn1 was localized to retinal NV. Compared to intravitreous injection of BSA at P12 (0.1994±0.0708, n=8,), intravitreous injection of 400ng (0.0734±0.0299, n=12, p=0.0027) or 800ng (0.1366±0.0159, n=8, p=0.031) of sNpn1 resulted in significantly less retinal NV at P17. Conclusions: There is increased expression of Npn1 in neovascular tissue in the retina. Intravitreous injection of sNpn1 suppresses the development of retinal NV in mice with ischemic retinopathy. Signaling through Npn1 may contribute to retinal NV in ischemic retinopathy and sNpn1suppresses retinal NV, probably by sequestering VEGF.
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