Neuropilin-1–expressing microglia are associated with nascent retinal vasculature yet dispensable for developmental angiogenesis

Abstract

Purpose: Neuropilin-1 (NRP-1) is a transmembrane receptor that is critical for vascular development within the central nervous system (CNS). It binds and influences signaling of several key angiogenic factors, such as VEGF-165, semaphorin 3A, platelet derived growth factor, and more. Neuropilin-1 is expressed by neurons and endothelial cells as well as a subpopulation of proangiogenic macrophages/microglia that are thought to interact with endothelial tip cells to promote vascular anastomosis during brain vascularization. We previously demonstrated a significant role for NRP-1 in macrophage chemotaxis and showed that NRP-1–expressing microglia are major contributors to pathologic retinal angiogenesis. Given this influence on CNS angiogenesis, we now investigated the involvement of microglia-resident NRP-1 in developmental retinal vascularization. Methods: We followed NRP-1 expressing microglia during retinal development. We used LysM -cre myeloid lineage-driver cre mice to reduce expression of NRP-1 in retinal myeloid-derived cells and performed a comprehensive morphometric analysis of retinal vasculature during development. Results: We provide evidence that NRP-1+ microglia are present throughout the retina during vascular development with a preference for the non-vascularized retina. Using LysM-Cre/Nrp1fl/fl mice, we reduced NRP-1 expression by ~65% in retinal microglia and demonstrate that deficiency in NRP-1 in these microglia does not impair retinal angiogenesis. Conclusions: Our data draw a dichotomous role for NRP-1 in cells of myeloid lineage where it is dispensable for adequate retinal developmental vascularization yet obligate for pathologic retinal angiogenesis.