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M.E. Hartnett, A. Lappas, D.C. Darland, J.R. McColm, P.A. D'Amore; Endothelial Cells in Close Proximity to Retinal Pigment Epithelium Causes Outer Retinal Barrier Dysfunction via a Soluble VEGF-Dependent Mechanism . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3923.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To investigate the effect of endothelial cells (EC) on the barrier function of the retinal pigment epithelium (RPE). Methods: The barrier properties of primary bovine RPE, as measured by transepithelial electrical resistance (TER), were tested in contacting and non-contacting cocultures of RPE and bovine EC. The conditioned media of cocultures were analyzed for soluble vascular endothelial growth factor (VEGF) by ELISA. A neutralizing antibody to VEGF165 was added to cocultures of RPE and EC and the TER was measured. Results: Compared to solo RPE culture, cocultivation of RPE with EC reduced RPE barrier function significantly and led to a greater release of soluble VEGF into the conditioned media (p<0.05). Neutralizing VEGF with antibody led to partial recovery of barrier properties in the coculture conditions (p<0.03). Conclusions: Cultivation of RPE with EC reduces RPE barrier properties and is, in part, mediated by soluble VEGF. This is relevant for ocular pathologies such as choroidal neovascularization, where EC move through Bruch's membrane and come into close proximity to or contact the RPE. The proximity of RPE and EC may lead to further exacerbation of the already compromised blood retinal barrier.
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