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Type: Journal article
Title: Stimulation of Aquaporin-Mediated Fluid Transport by Cyclic GMP in Human Retinal Pigment Epithelium In Vitro
Author: Baetz, N.
Stamer, W.
Yool, A.
Citation: Investigative Ophthalmology and Visual Science, 2012; 53(4):2127-2132
Publisher: Assoc Research Vision Ophthalmology Inc
Issue Date: 2012
ISSN: 0146-0404
Statement of
Nicholas W. Baetz, W. Daniel Stamer and Andrea J. Yool
Abstract: <h4>Purpose</h4>The retinal pigment epithelium (RPE) expresses aquaporin-1 (AQP1) and components of the natriuretic peptide signaling pathway. We hypothesized that stimulation of the natriuretic signaling pathway in RPE with atrial natriuretic peptide (ANP) and with membrane-permeable analogs of cGMP would induce a net apical-to-basal transport of fluid.<h4>Methods</h4>The hypothesis was tested using human RPE cultures that retain properties seen in vivo. Confluent monolayers were treated with ANP or membrane-permeable cGMP analogs in the presence of anantin, H-8, and an AQP1 inhibitor, AqB013. Fluid movement from the apical to basal chambers was measured by weight and used to calculate net fluid transport.<h4>Results</h4>Our results demonstrated a 40% increase in net apical-to-basal fluid transport by ANP (5 μM) that was inhibited completely by the ANP receptor antagonist anantin and a 60% increase in net apical-to-basal fluid transport in response to the extracellularly applied membrane-permeable cGMP analog pCPT-cGMP (50 μM), which was not affected by the protein kinase G inhibitor H-8. The aquaporin antagonist AqB013 (20 μM) inhibited the cGMP-stimulated RPE fluid flux.<h4>Conclusions</h4>The effect of cGMP is consistent with an enhancement of the net fluid flux in RPE mediated by AQP1 channels. Pharmacologic activation of cGMP signaling and concomitant stimulation of fluid uptake from the subretinal space could offer insights into a new approach to treating or reducing the risk of retinal detachment.
Keywords: Cells, Cultured
Xenopus laevis
Peptides, Cyclic
Atrial Natriuretic Factor
Cyclic GMP-Dependent Protein Kinases
Cyclic GMP
Blotting, Western
Cell Membrane Permeability
Biological Transport, Active
Dose-Response Relationship, Drug
Aquaporin 1
Retinal Pigment Epithelium
Rights: Copyright © Association for Research in Vision and Ophthalmology
DOI: 10.1167/iovs.11-8471
Published version:
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Physiology publications

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