Deficiency of Neuropilin 2 Suppresses VEGF-Induced Retinal Neovascularization

Jikui Shen,Xiaoling Liang,Rebecca Samul,Peter A Campochiaro,Joelle Zimmer,Hansheng Liu,Sean Hackett

doi:10.2119/2004-00017.campochiaro

Jikui Shen, Xiaoling Liang + Show 5 more

Open Access

https://doi.org/10.2119/2004-00017.campochiaro

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Abstract

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.

Highlights

There is compelling evidence indicating that vascular endothelial growth factor (VEGF) plays a central role in the development of retinal and choroidal neovascularization (NV)
The Npn2 staining colocalized with Griffonia simplicifolia lectin B4 (GSA), demonstrating that the Npn2 was present in retinal NV
Most studies utilizing in vitro testing suggest that VEGF receptor 2 plays a predominant role in VEGF-induced endothelial cell proliferation and NV

Summary

Introduction

There is compelling evidence indicating that vascular endothelial growth factor (VEGF) plays a central role in the development of retinal and choroidal neovascularization (NV) (for review, see 1). This has led to clinical trials testing the effects of VEGF antagonists in patients with subfoveal choroidal NV due to age-related macular degeneration. In this regard, it is valuable to obtain clues from mechanisms identified in other vascular beds, while at the same time understanding that all inferences must be directly tested in the vascular beds of the eye

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