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Victor H Guaiquil, Zan Pan, Natalia Karagianni, Paula Carcamo, Gemstonn Alegre, Mark Rosenblatt; Vascular Endothelial Growth Factor-A and -B induced differential neuronal growth of cornea derived peripheral neurons. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):718.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the intracellular signaling pathways involved in VEGF-induced cornea nerve regeneration
To evaluate the mechanisms by which VEGF-A and VEGF-B induced nerve regeneration, we treated isolated trigeminal ganglia (TG) neuronal cells from Thy1-YFP mice and rat PC12 neuronal cell line with VEGF-A and -B and analyzed the neurite- induced growth in a time and dose dependent manner. We performed RNA seq analysis to determine the differential gene expression induced by both growth factors, as well as, inhibition studies to characterize the receptors activated by the ligands and the intracellular mediators involved in the differential phenotypic response leading to either neurite elongation or branching. We blocked the activation of VEGF receptors 1, and 2 and the neuropilin receptor and used specific inhibitors for the PI3K and Notch pathways and determined their effect on neurite growth
Both VEGF-A and VEGF-B induced neuronal growth in isolated trigeminal ganglia neurons as well as in PC12 cells. VEGF-A induced mostly TG neurite elongation while VEGF-B induced increased neurite branching. RNA seq analysis showed that there is a differential gene expression on TG neurons treated with VEGF-A or -B. Inhibition studies showed that VEGF-A activates VEGFR1, R2 and NRP1 receptors while VEGF-B only activate VEGFR1 and NRP1 receptors in both TG neurons and PC12 cells. Blocking the PI3K and Notch pathway inhibited the VEGF-A or -B induced neurite growth in TG cells
VEGF-A and -B can selectively and potently enhance neurite growth, they used specific receptors and similar intracellular mediators that resulted in increased neurite elongation and branching. Further studies are required to determine how the differential gene expression observed upon VEGF-A or -B treatment results in selected neuronal phenotypes that can enhance nerve regeneration in the cornea.
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