VEGF as a Paracrine Regulator of Conventional Outflow Facility.
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ABSTRACT: Purpose
Vascular endothelial growth factor (VEGF) regulates microvascular endothelial permeability, and the permeability of Schlemm's canal (SC) endothelium influences conventional aqueous humor outflow. We hypothesize that VEGF signaling regulates outflow facility.Methods
We measured outflow facility (C) in enucleated mouse eyes perfused with VEGF-A164a, VEGF-A165b, VEGF-D, or inhibitors to VEGF receptor 2 (VEGFR-2). We monitored VEGF-A secretion from human trabecular meshwork (TM) cells by ELISA after 24 hours of static culture or cyclic stretch. We used immunofluorescence microscopy to localize VEGF-A protein within the TM of mice.Results
VEGF-A164a increased C in enucleated mouse eyes. Cyclic stretch increased VEGF-A secretion by human TM cells, which corresponded to VEGF-A localization in the TM of mice. Blockade of VEGFR-2 decreased C, using either of the inhibitors SU5416 or Ki8751 or the inactive splice variant VEGF-A165b. VEGF-D increased C, which could be blocked by Ki8751.Conclusions
VEGF is a paracrine regulator of conventional outflow facility that is secreted by TM cells in response to mechanical stress. VEGF affects facility via VEGFR-2 likely at the level of SC endothelium. Disruption of VEGF signaling in the TM may explain why anti-VEGF therapy is associated with decreased outflow facility and sustained ocular hypertension.
SUBMITTER: Reina-Torres E
PROVIDER: S-EPMC5374885 | biostudies-literature | 2017 Mar
REPOSITORIES: biostudies-literature
Publications
VEGF as a Paracrine Regulator of Conventional Outflow Facility.
Reina-Torres Ester E Wen Joanne C JC Liu Katy C KC Li Guorong G Sherwood Joseph M JM Chang Jason Y H JY Challa Pratap P Flügel-Koch Cassandra M CM Stamer W Daniel WD Allingham R Rand RR Overby Darryl R DR
Investigative ophthalmology & visual science 20170301 3
<h4>Purpose</h4>Vascular endothelial growth factor (VEGF) regulates microvascular endothelial permeability, and the permeability of Schlemm's canal (SC) endothelium influences conventional aqueous humor outflow. We hypothesize that VEGF signaling regulates outflow facility.<h4>Methods</h4>We measured outflow facility (C) in enucleated mouse eyes perfused with VEGF-A164a, VEGF-A165b, VEGF-D, or inhibitors to VEGF receptor 2 (VEGFR-2). We monitored VEGF-A secretion from human trabecular meshwork ( ...[more]
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