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qiang zhou, Victor H Guaiquil, Yun Cin Luo, Michael Sun, Mark Rosenblatt; Effects of Vascular Endothelial Growth Factor-A and -B on angiogenesis and nerve regeneration of the cornea. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3531. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To study the dose dependent effect of VEGF-induced endothelial and neuronal cell growth.
To characterize the differential outcomes by which VEGF-A and VEGF-B induced angiogenesis and cornea nerve regeneration, we study the effects of VEGF-A and -B on in vitro angiogenesis assays (cell proliferation, wound healing and tube formation) using mouse aortic endothelial cells (MAEC), as well as in vivo, using a cornea micro pellet method in which growth factor are slowly released into the cornea stroma. The blood vessel growth was traced using Image J software on Cd31 stained immunofluorescence flat mount corneas as well as in images taken in vivo. Nerve growth was traced using Neurolucida software on flat mount corneas stained with B3 tubulin.
VEGF-A is a well known angiogenic factor, however at the dose used for nerve regeneration it does not induce blood vessel growth. In vitro, we found that both VEGF-A and VEGF-B induced MAEC cell proliferation, increased wound healing and tube formation independently of the dose administered. However, in vivo only VEGF-A used at 150 ng/ml induced significant blood vessel growth in the corneas treated with growth factor loaded pellets. VEGF-B used at this same dose not induce any visible angiogenesis. Similarly, both ligands used at the lower dose of 50 ng/ml which is a potent dose for nerve regeneration, does not induce neovascularization.
VEGF-A and -B can selectively and potently enhance neurite growth, but only VEGFA at high dose is a potent inducer of angiogenesis. VEGF-B appears as a potent and specific nerve regeneration inducer and may provide a better therapeutic to avoid unwanted angiogenesis in the injured cornea.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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