Deficiency of Neuropilin 2 Suppresses VEGF-Induced Retinal Neovascularization
Vascular endothelial growth factor (VEGF) plays a central role in the development of ocular neovascularization (NV) and is an excellent target for therapeutic intervention. VEGF acts through several receptors, including VEGF receptor 1, VEGF receptor 2, neuropilin-1 (Npn1), and Npn2, but the exact role of these receptors in the development of retinal NV is unknown. In this study, we investigated the expression of npn2 mRNA during new blood vessel growth in the retina and used npn2 knockout mice to assess the impact of deficiency of Npn2 on retinal NV. The level of npn2 mRNA in the retina increased during retinal vascular development, after exposure to hyperoxia, and after the onset of retinal ischemia. Immunohistochemistry showed colocalization of Npn2 with a vascular marker in retinal NV. Compared with littermate controls, mice deficient in Npn2 had significantly less ischemia-induced retinal NV and very little subretinal NV due to expression of a Vegf transgene. These data suggest that Npn2 facilitates VEGF-induced retinal NV and may constitute a useful target for therapeutic intervention in ocular diseases complicated by NV.
The authors thank David Ginty, PhD, and Alex Kolodkin, PhD, for generously providing npn−/− mice. This work was supported by EY05951, EY12609, and core grant P30EY1765 from the National Eye Institute; Research to Prevent Blindness Inc (a Lew R Wasserman Merit Award [PAC]); and Dr and Mrs William Lake. PAC is the George S and Dolores Dore Eccles Professor of Ophthalmology.
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