Inhibition of Cx43 gap junction uncoupling prevents high glucose-induced apoptosis and reduces excess cell monolayer permeability in retinal vascular endothelial cells

Experimental Eye Research
Dongjoon KimSayon Roy

Abstract

The aim of this study was to investigate whether inhibition of connexin 43 gap junction-uncoupling is sufficient to prevent retinal vascular cell loss under high glucose condition and reduce cell monolayer permeability. Rat retinal endothelial cells were grown for 3, 5, and 7 days in normal (5 mM) or high glucose (30 mM) medium; in parallel, cells grown in high glucose medium were exposed for 3, 5, and 7 days to 100 nM danegaptide, which stabilizes connexin 43-mediated cell coupling. Additionally, cells grown in normal medium were treated with a connexin 43 blocker as a negative control. To determine gap junction intercellular communication, scrape load dye transfer assay was performed at the three time points. Cells were assessed for apoptosis and cell monolayer permeability by differential dye staining and in vitro permeability assays, respectively. Cells treated with danegaptide preserved gap junction intercellular communication, decreased cell death, and reduced cell monolayer permeability. Scrape load dye transfer assay indicated that cells exposed to danegaptide for 3, 5, and 7 days under high glucose condition maintained gap junction intercellular communication. Importantly, danegaptide significantly prevented high gluco...Continue Reading

Citations

Aug 12, 2020·Visual Neuroscience·Cyril G EleftheriouBotir T Sagdullaev
Aug 16, 2019·Investigative Ophthalmology & Visual Science·Keith D RochfortPhilip M Cummins
Dec 22, 2020·Seizure : the Journal of the British Epilepsy Association·Ting-Ting YangFeng-Ru Tang
Dec 6, 2020·Particle and Fibre Toxicology·Shuang LiangZhiwei Sun
Jan 12, 2021·Frontiers in Oncology·Kai-Jun LuoJean X Jiang
Apr 4, 2021·International Journal of Molecular Sciences·Jorge González-CasanovaDiana Rojas-Gomez
Apr 4, 2021·International Journal of Molecular Sciences·Paul E SquiresClaire E Hills

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis