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Mediators of Inflammation
Volume 2017 (2017), Article ID 3164375, 16 pages
Research Article

Molecular Responses of Human Retinal Cells to Infection with Dengue Virus

1Microbiology & Infectious Diseases, Flinders University School of Medicine, Rm 5D-316, 1 Flinders Drive, Bedford Park, Adelaide, SA 5042, Australia
2Eye & Vision Health, Flinders University School of Medicine, Rm 4E-431, 1 Flinders Drive, Bedford Park, Adelaide, SA 5042, Australia
3Flinders Centre for Innovation in Cancer, Flinders University School of Medicine, 1 Flinders Drive, Bedford Park, Adelaide, SA 5042, Australia
4Ocular Inflammation and Immunology Service, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore 168751

Correspondence should be addressed to Justine R. Smith

Received 27 April 2017; Revised 22 August 2017; Accepted 6 September 2017; Published 12 November 2017

Academic Editor: Giuseppe Valacchi

Copyright © 2017 Jillian M. Carr et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Recent clinical reports indicate that infection with dengue virus (DENV) commonly has ocular manifestations. The most serious threat to vision is dengue retinopathy, including retinal vasculopathy and macular edema. Mechanisms of retinopathy are unstudied, but observations in patients implicate retinal pigment epithelial cells and retinal endothelial cells. Human retinal cells were inoculated with DENV-2 and monitored for up to 72 hours. Epithelial and endothelial cells supported DENV replication and release, but epithelial cells alone demonstrated clear cytopathic effect, and infection was more productive in those cells. Infection induced type I interferon responses from both cells, but this was stronger in epithelial cells. Endothelial cells increased expression of adhesion molecules, with sustained overexpression of vascular adhesion molecule-1. Transcellular impedance decreased for epithelial monolayers, but not endothelial monolayers, coinciding with cytopathic effect. This reduction was accompanied by disorganization of intracellular filamentous-actin and decreased expression of junctional molecules, zonula occludens 1, and catenin-β1. Changes in endothelial expression of adhesion molecules are consistent with the retinal vasculopathy seen in patients infected with DENV; decreases in epithelial junctional protein expression, paralleling loss of integrity of the epithelium, provide a molecular basis for DENV-associated macular edema. These molecular processes present potential therapeutic targets for vision-threatening dengue retinopathy.