Stimulation of aquaporin-mediated fluid transport by cyclic GMP in human retinal pigment epithelium in vitro.

Journal Article (Journal Article)

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Full Text

Duke Authors

Cited Authors

  • Baetz, NW; Stamer, WD; Yool, AJ

Published Date

  • April 24, 2012

Published In

Volume / Issue

  • 53 / 4

Start / End Page

  • 2127 - 2132

PubMed ID

  • 22427546

Pubmed Central ID

  • PMC3995571

Electronic International Standard Serial Number (EISSN)

  • 1552-5783

Digital Object Identifier (DOI)

  • 10.1167/iovs.11-8471


  • eng

Conference Location

  • United States