Journal article
Assessing the Effects of Ripasudil, a Novel Rho Kinase Inhibitor, on Human Corneal Endothelial Cell Health
Journal of ocular pharmacology and therapeutics, Vol.34(10), pp.692-699
12/01/2018
DOI: 10.1089/jop.2018.0063
PMID: 30312120
Abstract
Purpose: To determine how the Rho kinase inhibitor, ripasudil, affects metabolic function and cell viability in donor human corneal endothelial cells (HCECs). Methods: Endothelial cell-Descemet membrane (EDM) tissues were treated with 10 μM ripasudil and assayed for mitochondrial and glycolytic activity using extracellular flux analysis and then compared to untreated controls. In addition, EDM tissues with a 24-h ripasudil treatment and control tissues were exposed to 1 μM staurosporine to induce apoptosis and then analyzed for cell viability using apoptosis and necrosis assays. Results: Mitochondrial respiration metrics, specifically maximal respiration ( P = 0.758) and spare respiratory capacity ( P = 0.777), did not differ among the 1-h ripasudil treatment, 24-h treatment, and untreated tissues. Glycolytic activity assays showed an increase in glycolytic capacity at 1 h compared to the 24-h exposure group ( P = 0.049) and controls ( P = 0.009). Following exposure to staurosporine, the percentage of apoptotic HCECs was lower ( P = 0.009) in ripasudil-treated tissues (2.473%, standard error of the mean [SEM] 0.477%) compared to untreated controls (3.349%, SEM 0.566%). In contrast, the percentage of necrotic HCECs decreased but did not differ statistically ( P = 0.158) between ripasudil-treated (3.789%, SEM 0.487%) and untreated (4.567%, SEM 0.571%) tissues. Conclusions: Exposures to ripasudil did not result in any detectable reduction in metabolic function for HCECs in an ex vivo donor tissue model, and an increase in glycolytic activity at the 1-h time point was detected. In addition, HCECs treated with ripasudil gained a protective effect against induced apoptosis, suggesting that ripasudil may help improve the integrity of the corneal endothelium.
Details
- Title: Subtitle
- Assessing the Effects of Ripasudil, a Novel Rho Kinase Inhibitor, on Human Corneal Endothelial Cell Health
- Creators
- Andrew S Goldstein - 2Iowa Lions Eye Bank, Coralville, IowaBenjamin T Aldrich - 2Iowa Lions Eye Bank, Coralville, IowaJessica M Skeie - 2Iowa Lions Eye Bank, Coralville, IowaGregory A Schmidt - 2Iowa Lions Eye Bank, Coralville, IowaCynthia R Reed - 2Iowa Lions Eye Bank, Coralville, IowaM. Bridget Zimmerman - 3Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IowaMark A Greiner - 2Iowa Lions Eye Bank, Coralville, Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of ocular pharmacology and therapeutics, Vol.34(10), pp.692-699
- Publisher
- Mary Ann Liebert, Inc., publishers
- DOI
- 10.1089/jop.2018.0063
- PMID
- 30312120
- ISSN
- 1080-7683
- eISSN
- 1557-7732
- Language
- English
- Date published
- 12/01/2018
- Academic Unit
- Biostatistics; Ophthalmology and Visual Sciences
- Record Identifier
- 9983980077802771
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