PlGF and VEGF-A/PlGF Heterodimer are Crucial for Recruitment and Activation of Immune Cells During Choroid Neovascularization.

Autor:	Tarallo V; Angiogenesis Lab, Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso' - CNR, Naples, Italy., Magliacane Trotta S; Angiogenesis Lab, Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso' - CNR, Naples, Italy., Panico S; Angiogenesis Lab, Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso' - CNR, Naples, Italy., D'Orsi L; Angiogenesis Lab, Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso' - CNR, Naples, Italy.; BIOVIIIx srl, Via Alessandro Manzoni 1, Napoli, Italy., Mercadante G; Angiogenesis Lab, Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso' - CNR, Naples, Italy., Cicatiello V; Angiogenesis Lab, Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso' - CNR, Naples, Italy., De Falco S; Angiogenesis Lab, Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso' - CNR, Naples, Italy.; BIOVIIIx srl, Via Alessandro Manzoni 1, Napoli, Italy.; AnBition srl, Via Alessandro Manzoni 1, Napoli, Italy.
Jazyk:	angličtina
Zdroj:	Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2024 Jul 01; Vol. 65 (8), pp. 12.
DOI:	10.1167/iovs.65.8.12
Abstrakt:	Purpose: Recruitment and activation of inflammatory cells, such as retinal microglia/macrophages, in the subretinal space contribute significantly to the pathogenesis of age-related macular degeneration (AMD). This study aims to explore the functional role of vascular endothelial growth factor (VEGF-A), placental growth factor (PlGF) and VEGF-A/PlGF heterodimer in immune homeostasis and activation during pathological laser-induced choroidal neovascularization (CNV). Methods: To investigate these roles, we utilized the PlGF-DE knockin (KI) mouse model, which is the full functional knockout (KO) of PlGF. In this model, mice express a variant of PlGF, named PlGF-DE, that is unable to bind and activate VEGFR-1 but can still form heterodimer with VEGF-A. Results: Our findings demonstrate that, although 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 VEGF-A/PlGF heterodimer in PlGF-DE-KI mice rescued the immune cell response at the early phase of CNV compared to VEGF-A delivery. Conclusions: In summary, our study suggests that targeting PlGF and the VEGF-A/PlGF heterodimer, thereby preventing VEGFR-1 activation, could represent a potential therapeutic approach for the management of inflammatory processes in diseases such as AMD.
Databáze:	MEDLINE
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