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Dimitrios Karamichos, Jesper Hjortdal, Audrey E K Hutcheon, John M Asara, James D Zieske; Metabolic defects and oxidative stress in keratoconus. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1001.
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© ARVO (1962-2015); The Authors (2016-present)
Corneal bulging, stromal thinning and scarring are three of the main characteristics of the Keratoconus (KC) disorder. KC in most cases appears in early adulthood and can progress rapidly resulting in severe vision loss. Its prevalence ranges from 4-600/100,000 people worldwide. While efforts have been made over the years, the exact cause of the disease remains unknown. The aim of this study was to identify alterations in endogenous metabolites in the tears of KC patients depending on treatment.
16 patients were included in this study and monitored using Pentacam tomography. Human tears were collected from healthy individuals and KC patients with different treatments. Three groups were tested: 1) Age-matched controls with no eye disease, 2) KC - No Correction, and 3) KC - Rigid Gas permeable lenses. All samples were processed for metabolomic analysis using LC-MS/MS.
We evaluated 16 patients, 12 of which have been diagnosed with KC. Ages ranged between 20-53 y/o with maximum keratometric (Kmax) values of 44.9 - 63.7. We identified a total of 296 different metabolites of which >30 were significantly regulated between groups. The citric acid cycle included some of the affected metabolites that had notable changes, such as Fumarate, which had a ~4-fold upregulation in Group 2 and a 2-fold downregulation in Group 3 when compared to Healthy-No KC (Group 1). Also, Oxaloacetate had an ~2-fold downregulation in both Groups 2 and 3 when compared to Group 1. The oxidation state (redox) was also severely affected. Group 2 was under severe oxidative stress causing multiple metabolites to become upregulated when compared to the other Groups. Lactate and Arginine are just two of the significantly regulated metabolites related to redox. Lactate and Arginine levels were elevated 7 and 4 fold, respectively, in Group 2 compared to the others. Glutathione exists in both reduced (GSH) and oxidized (GSSG) states. A decreased GSH-to-GSSG ratio is considered indicative of oxidative stress; Group 2 showed 4-fold downregulation when compared to others, indicating significant oxidative stress levels.
Overall, our data supports the growing consensus that levels of metabolites are predictive for particular processes and conditions. These in vivo data showed clear links with our in vitro findings as well as indicating metabolism alterations in the tears of KC patients dependent on treatment.
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