PlGF and VEGF-A/PlGF heterodimer are crucial in the recruitment and activation of immune cells during choroidal neovascularization

Author:

Tarallo Valeria1,Trotta Sara Magliacane1,Panico Sonia1,D’Orsi Luca2,Mercadante Grazia1,Cicatiello Valeria1,Falco Sandro1

Affiliation:

1. Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’ - CNR

2. BIOVIIIx srl

Abstract

Abstract Recruitment and activation of inflammatory cells, such as retinal microglia/macrophages, in the sub-retinal space contribute significantly to the pathogenesis of age-related macular degeneration (AMD). In this study, we utilized the full functional knockout of placental growth factor (PlGF), the PlGF-DE knockin mouse, to investigate the functional role of vascular endothelial growth factor (VEGF-A), PlGF and VEGF-A/PlGF heterodimer in immune homeostasis and activation during pathological laser-induced choroidal neovascularization (CNV). Our findings demonstrate that, while there is no difference in healthy conditions, PlGF-DE-Ki mice exhibit decreased microglia reactivity and reduced recruitment of both microglia and monocyte-macrophages, compared to wild-type mice during laser-induced CNV. This impairment is associated with a reduction in VEGF receptor 1 (VEGFR-1) phosphorylation in the retinae of PlGF-DE-Ki mice compared to C57Bl6/J mice. Corroborating these data, intravitreal delivery of PlGF or the heterodimer in PlGF-DE-Ki mice rescued the immune cell response at the early phase of CNV compared to VEGF-A delivery. In summary, our study suggests that targeting PlGF and the VEGF-A/PlGF heterodimer thereby preventing VEGFR-1 activation could represents a potential therapeutic approach for the management of inflammatory processes in diseases such as AMD.

Publisher

Research Square Platform LLC

Reference32 articles.

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