VEGF as a paracrine regulator of conventional outflow facility

13Citations
Citations of this article
20Readers
Mendeley users who have this article in their library.

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-A164 a 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.

Cite

CITATION STYLE

APA

Reina-Torres, E., Wen, J. C., Liu, K. C., Li, G., Sherwood, J. M., Chang, J. Y. H., … Overby, D. R. (2017). VEGF as a paracrine regulator of conventional outflow facility. Investigative Ophthalmology and Visual Science, 58(3), 1899–1908. https://doi.org/10.1167/iovs.16-20779

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free