Complete metabolome and lipidome analysis reveals novel biomarkers in the human diabetic corneal stroma

Shrestha Priyadarsini, Tina B. McKay, Akhee Sarker-Nag, Jeremy Allegood, Charles Chalfant, Jian Xing Ma, Dimitrios Karamichos

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Prolonged hyperglycemia during diabetes mellitus can cause severe ophthalmic complications affecting both the anterior and posterior ocular segments leading to impaired vision or blindness. Diabetes-induced corneal pathologies are associated with decreased wound healing capacity, corneal edema, and altered epithelial basement membrane. The mechanism by which diabetes modulates structure and function within the corneal stroma are unknown. In our study, we characterized the effects of diabetes on extracellular matrix, lipid transport, and cellular metabolism by defining the entire metabolome and lipidome of Type 1 and Type 2 human diabetic corneal stroma. Significant increases in Collagen I and III were found in diabetic corneas suggesting that diabetes promotes defects in matrix structure leading to scarring. Furthermore, increased lipid content, including sphingosine-1-phosphate and dihydrosphingosine, in diabetic corneas compared to healthy controls were measured suggesting altered lipid retention. Metabolomics analysis identified elevated tryptophan metabolites, independent of glucose metabolism, which correlated with upregulation of the Kynurenine pathway in diabetic corneas. We also found significant upregulation of novel biomarkers aminoadipic acid, D,L-pipecolic acid, and dihydroorotate. Our study links aberrant tryptophan metabolism to end-stage pathologies associated with diabetes indicating the potential of the Kynurenine pathway as a therapeutic target for inhibiting diabetes-associated defects in the eye.

Original languageEnglish
Pages (from-to)90-100
Number of pages11
JournalExperimental eye research
Volume153
DOIs
StatePublished - 1 Dec 2016

Keywords

  • Cellular metabolism
  • Corneal fibrosis
  • Diabetes mellitus
  • Kynurenine
  • Lipidomics

Fingerprint Dive into the research topics of 'Complete metabolome and lipidome analysis reveals novel biomarkers in the human diabetic corneal stroma'. Together they form a unique fingerprint.

  • Cite this