title: Quercetin modulates keratoconus metabolism in vitro.
abstract: Corneal scarring is the result of a disease, infection or injury. The resulting scars cause significant loss of vision or even blindness. To-date, the most successful treatment is corneal transplantation, but it does not come without side effects. One of the corneal dystrophies that are correlated with corneal scarring is keratoconus (KC). The onset of the disease is still unknown; however, altered cellular metabolism has been linked to promoting the fibrotic phenotype and therefore scarring. We have previously shown that human keratoconus cells (HKCs) have altered metabolic activity when compared to normal human corneal fibroblasts (HCFs). In our current study, we present evidence that quercetin, a natural flavonoid, is a strong candidate for regulating metabolic activity of both HCFs and HKCs in vitro and therefore a potential therapeutic to target the altered cellular metabolism characteristic of HKCs. Targeted mass spectrometry-based metabolomics was performed on HCFs and HKCs with and without quercetin treatment in order to identify variations in metabolite flux. Overall, our study reveals a novel therapeutic target OF Quercetin on corneal stromal cell metabolism in both healthy and diseased states. Clearly, further studies are necessary in order to dissect the mechanism of action of quercetin.
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Tina B
authors.initials: TB
authors.lastname: McKay
authors.affiliation: Department of Ophthalmology/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Akhee
authors.initials: A
authors.lastname: Sarker-Nag
authors.affiliation: Department of Ophthalmology/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Desiree'
authors.initials: D
authors.lastname: Lyon
authors.affiliation: Division of Signal Transduction, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, MA, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Asara
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.|Department of Ophthalmology/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Karamichos
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D003315:Cornea / Q000166:cytology; D004734:Energy Metabolism / Q000187:drug effects; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007640:Keratoconus / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D061251:Primary Cell Culture; D011794:Quercetin / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D011794:Quercetin
keywords: cell metabolism; cornea; fibrosis; keratoconus; metabolomics; quercetin; urea cycle