Abstract
PurposeAnti-vascular endothelial growth factor (VEGF) antibody therapy is an effective treatment for ocular angiogenesis. Although the intraocular pressure of some patients increases after anti-VEGF therapy, the effects of VEGF-A on the aqueous humor outflow pathway remain unknown. This study investigated the effects of VEGF-A on the aqueous humor outflow pathway.MethodsWe used human recombinant VEGF121 and VEGF165. Trabecular meshwork (TM) and Schlemm’s canal endothelial (SCE) cells were isolated from the eyes of cynomolgus monkeys. Expression of mRNA coding four VEGF receptors, VEGFR1 (FLT1), VEGFR2 (KDR), neuropilin-1, and neuropilin-2, was examined by RT-PCR. To evaluate the permeability of cell monolayers, we measured transendothelial electrical resistance (TEER). The outflow facility was measured in perfused porcine anterior segment organ cultures treated with 30 ng/mL VEGF121 for 48 h.ResultsFour VEGF-A-related receptor mRNAs were expressed in TM and SCE cells. The TEER of TM cells was not significantly affected by VEGF121 or VEGF165 treatment. In contrast, the TEER of SCE cells was significantly lower 48 h after treatment with 30 ng/mL VEGF121 to 69.4 ± 12.2% of baseline (n = 10), which was a significant difference compared with the control (P = 0.0001). VEGF165 (30 ng/mL) decreased the TEER of SCE cells at 48 h after treatment to 72.3 ± 14.1% compared with the baseline (n = 10), which was not a significant difference compared with the control (P = 0.0935). Ki8751, a selective VEGFR2 inhibitor, completely suppressed the effect of VEGF121 on SCE cell permeability, although ZM306416, a selective VEGFR1 inhibitor, did not affect the VEGF121-induced decrease in TEER. Perfusion with 30 ng/mL of VEGF121 for 48 h significantly increased the outflow facility compared with the control (47.8 ± 28.5%, n = 5, P = 0.013).ConclusionsThese results suggest that VEGF-A may regulate the conventional aqueous outflow of SCE cells through VEGFR2.
Highlights
Vascular endothelial growth factors (VEGFs) consist of five related growth factors in mammals: vascular endothelial growth factor (VEGF)-A, VEGF-B, VEGF-C, VEGF-D, and placental growth factor
Four VEGF-A-related receptor mRNAs were expressed in Trabecular meshwork (TM) and s canal endothelial (SCE) cells
The transendothelial electrical resistance (TEER) of SCE cells was significantly lower 48 h after treatment with 30 ng/mL VEGF121 to 69.4 ± 12.2% of baseline (n = 10), which was a significant difference compared with the control (P = 0.0001)
Summary
Vascular endothelial growth factors (VEGFs) consist of five related growth factors in mammals: VEGF-A, VEGF-B, VEGF-C, VEGF-D, and placental growth factor. VEGFs regulate the physiological functions of vascular and lymphatic vessels. These effects of VEGFs are regulated by three receptor tyrosine kinases including VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4), and by co-receptors, such as neuropilins [1]. VEGF-A induces the most potent angiogenic response among the VEGFs, and the effects of VEGF-A are regulated through VEGFR1, VEGFR2, and neuropilins. Abnormal angiogenesis is associated with several diseases including cancer, inflammatory diseases, and age-related macular degeneration (AMD) [2]. Previous studies have reported that intraocular concentrations of VEGF-A were increased in AMD patients [3]. Intraocular pressure (IOP) elevation after anti-VEGF treatment has been reported by many clinicians [7,8,9,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
