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Tomokazu Fujimoto, Toshihiro Inoue, KEI MAKI, Miyuki Mochita Inoue, Hidenobu Tanihara; Vascular Endothelial Growth Factor-A Increases Aqueous humor Outflow Fcility. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4689.
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© ARVO (1962-2015); The Authors (2016-present)
The purpose of this study is to investigate the vascular endothelial growth factor (VEGF)-A effects on aqueous humor outflow pathway.
We used human recombinant VEGF121 and VEGF165 protein in this study. Trabecular meshwork (TM) and Schlemm’s canal endothelial (SCE) cells were isolated from the eyes of cynomolgus monkeys. Expression of four VEGF receptors mRNA, VEGFR1 (FLT1), VEGFR2 (KDR), neuropilin1 (NRP1) and neuropilin 2 (NRP2), in TM and SCE cells were examined by RT-PCR. Permeability of monolayer of the cells was evaluated by measuring transendothelial electrical resistance (TEER). Outflow facility was measured in perfused porcine anterior segment organ cultures treated with 30 ng/mL VEGF121 for 48 hours.
VEGF-A related receptors’ mRNAs (FLT1, KDR, NRP1 and NRP2) were expressed in TM and SCE cells. The TEER of TM cell was not significantly affected by VEGF121 or VEGF165 treatment. By contrast, the TEER of SCE cell was significantly decreased after 48-hour treatment with 10 and 30 nM VEGF121 to 75.2 ± 12.9% (P = 0.0058) and 68.9 ± 13.8% (P = 0.0005), respectively, compared to baseline (n=8 each). VEGF165 (30 nM) decreased the TEER of SCE-cell 48 hours after treatment to 69.6 ± 14.7% compared to base line (n=8), which was not significant difference compared with control (P = 0.0831). Axitinib, a non-selective inhibitor of VEGF receptors, suppressed the effect of VEGF121 on SCE-cell permeability. Furthermore, Ki8751, a selective VEGFR2 inhibitor, completely suppressed the effect of VEGF121 on SCE-cell permeability. Perfusion with 30 ng/mL VEGF121 for 48 hours by anterior segment organ culture significantly increased outflow facility compared with control (47.8 ± 28.5% , n=5, P= 0.013).
These results suggest that VEGF-A may regulate the conventional aqueous outflow through the VEGFR2 on SCE cell.
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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