VEGF as a Paracrine Regulator of Conventional Outflow Facility

Reina-Torres E, Wen JC, Liu KC, Li G, Sherwood JM, Chang JYH, Challa P, Flügel-Koch C, Stamer WD, Allingham RR, Overby DR (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Investigative Ophthalmology & Visual Science Association for Research in Vision and Ophthalmology (ARVO)

Book Volume: 58

Pages Range: 1899-1908

Journal Issue: 3

DOI: 10.1167/iovs.16-20779

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.

Authors with CRIS profile

Cassandra Flügel-Koch Medizinische Fakultät

Involved external institutions

Imperial College London / The Imperial College of Science, Technology and Medicine GB United Kingdom (GB) Duke University US United States (USA) (US)

How to cite

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 & Visual Science, 58(3), 1899-1908. https://doi.org/10.1167/iovs.16-20779

MLA:

Reina-Torres, Ester, et al. "VEGF as a Paracrine Regulator of Conventional Outflow Facility." Investigative Ophthalmology & Visual Science 58.3 (2017): 1899-1908.

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