In vitro model suggests oxidative stress involved in keratoconus disease

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In vitro model suggests oxidative stress involved in keratoconus disease

Show simple item record Karamichos, D. en_US Hutcheon, A. E. K. en_US Rich, C. B. en_US Trinkaus-Randall, V. en_US Asara, J. M. en_US Zieske, J. D. en_US 2014-05-06T16:17:39Z 2014 en_US
dc.identifier.citation Karamichos, D., A. E. K. Hutcheon, C. B. Rich, V. Trinkaus-Randall, J. M. Asara, and J. D. Zieske. 2014. “In vitro model suggests oxidative stress involved in keratoconus disease.” Scientific Reports 4 (1): 4608. doi:10.1038/srep04608. en
dc.identifier.issn 2045-2322 en
dc.description.abstract Keratoconus (KC) affects 1:2000 people and is a disorder where cornea thins and assumes a conical shape. Advanced KC requires surgery to maintain vision. The role of oxidative stress in KC remains unclear. We aimed to identify oxidative stress levels between human corneal keratocytes (HCKs), fibroblasts (HCFs) and keratoconus cells (HKCs). Cells were cultured in 2D and 3D systems. Vitamin C (VitC) and TGF-β3 (T3) were used for 4 weeks to stimulate self-assembled extracellular matrix (ECM). No T3 used as controls. Samples were analyzed using qRT-PCR and metabolomics. qRT-PCR data showed low levels of collagen I and V, as well as keratocan for HKCs, indicating differentiation to a myofibroblast phenotype. Collagen type III, a marker for fibrosis, was up regulated in HKCs. We robustly detected more than 150 metabolites of the targeted 250 by LC-MS/MS per condition and among those metabolites several were related to oxidative stress. Lactate levels, lactate/malate and lactate/pyruvate ratios were elevated in HKCs, while arginine and glutathione/oxidized glutathione ratio were reduced. Similar patterns found in both 2D and 3D. Our data shows that fibroblasts exhibit enhanced oxidative stress compared to keratocytes. Furthermore the HKC cells exhibit the greatest level suggesting they may have a myofibroblast phenotype. en
dc.language.iso en_US en
dc.publisher Nature Publishing Group en
dc.relation.isversionof doi:10.1038/srep04608 en
dc.relation.hasversion en
dash.license LAA en_US
dc.title In vitro model suggests oxidative stress involved in keratoconus disease en
dc.type Journal Article en_US
dc.description.version Version of Record en
dc.relation.journal Scientific Reports en 2014-05-06T16:17:39Z

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