Caspase-14 Expression Impairs Retinal Pigment Epithelium Barrier Function: Potential Role in Diabetic Macular EdemaReport as inadecuate




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BioMed Research InternationalVolume 2014 2014, Article ID 417986, 11 pages

Research Article

Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University GRU, Augusta, GA 30912, USA

Oral Biology-Anatomy, College of Dental Medicine, GRU, Augusta, GA 30912, USA

Culver Vision Discovery Institute and Department of Ophthalmology, Medical College of Georgia, GRU, Augusta, GA 30912, USA

Department of Anatomy, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt

Department of Physiology, Medical College of Georgia, GRU and Charlie Norwood VA Medical Center, Augusta, GA 30912, USA

Departments of Ophthalmology and Visual Sciences and Biomedical Engineering, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA

Received 1 May 2014; Accepted 6 June 2014; Published 9 July 2014

Academic Editor: Wenbo Zhang

Copyright © 2014 Selina Beasley 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.

Abstract

We recently showed that caspase-14 is a novel molecule in retina with potential role in accelerated vascular cell death during diabetic retinopathy DR. Here, we evaluated whether caspase-14 is implicated in retinal pigment epithelial cells RPE dysfunction under hyperglycemia. The impact of high glucose HG, 30 mM D-glucose on caspase-14 expression in human RPE ARPE-19 cells was tested, which showed significant increase in caspase-14 expression compared with normal glucose 5 mM D-glucose + 25 mM L-glucose. We also evaluated the impact of modulating caspase-14 expression on RPE cells barrier function, phagocytosis, and activation of other caspases using ARPE-19 cells transfected with caspase-14 plasmid or caspase-14 siRNA. We used FITC-dextran flux assay and electric cell substrate impedance sensing ECIS to test the changes in RPE cell barrier function. Similar to HG, caspase-14 expression in ARPE-19 cells increased FITC-dextran leakage through the confluent monolayer and decreased the transcellular electrical resistance TER. These effects of HG were prevented by caspase-14 knockdown. Furthermore, caspase-14 knockdown prevented the HG-induced activation of caspase-1 and caspase-9, the only activated caspases by HG. Phagocytic activity was unaffected by caspase-14 expression. Our results suggest that caspase-14 contributes to RPE cell barrier disruption under hyperglycemic conditions and thus plays a role in the development of diabetic macular edema.





Author: Selina Beasley, Mohamed El-Sherbiny, Sylvia Megyerdi, Sally El-Shafey, Karishma Choksi, Ismail Kaddour-Djebbar, Nader Sheiba

Source: https://www.hindawi.com/



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