Pericyte Expression of VEGF-A Minimally Impacts Ocular Vascular Development and Neovascularization.

PubMed ID: 41002438

Author(s): Song YS, Wang S, Inampudi S, Risa H, Sorenson CM, Sheibani N. Pericyte Expression of VEGF-A Minimally Impacts Ocular Vascular Development and Neovascularization. Cells. 2025 Sep 21;14(18):1473. doi: 10.3390/cells14181473. PMID 41002438

Journal: Cells, Volume 14, Issue 18, Sep 2025

Pericytes produce vascular endothelial growth factor-A (VEGF-A; hereafter referred to as VEGF). VEGF inhibits pericyte proliferation and migration through enhanced VEGFR2 and PDGFRβ heterodimerization. Heterodimerization of these receptors on perivascular supporting cells, mediated by VEGF in culture, mitigates signaling through these receptors and promotes a quiescent phenotype. However, the detailed cellular mechanisms and the significance of these interactions in vivo require further investigation. The cell-autonomous activities of pericyte VEGF expression during vascular development and neovascularization remain unknown. Here we utilized mice conditionally lacking Vegfa in pericytes (VegfaPC) to examine its impact on retinal vascular development and pathological ocular neovascularization. Vascular integrity was also assessed in older mice using fundus imaging and fluorescein angiography. The lack of Vegfa pericyte expression delayed the initial spreading of the superficial layer of the retinal vasculature. Mice lacking Vegfa pericyte expression had similar numbers of retinal endothelial cells and arteries to their wild-type littermates. However, the number of pericytes was significantly reduced in younger VegfaPC mice but increased in more mature mice. In addition, pericyte Vegfa deficiency did not impact responses during oxygen-induced ischemic retinopathy and laser-induced choroidal neovascularization. Thus, pericyte VEGF expression plays a role during early stages of retinal vascular development with limited influence on mature retinal vascularization, its integrity, and neovascularization.