April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
High Glucose-Induced Gene Expression Associated with Oxidative Stress and PI3K Signaling in Diabetic Human Corneal Epithelial Cells
Author Affiliations & Notes
  • K. Xu
    Ophthalmology, Wayne State Univ/Kresge Eye Inst, Detroit, Michigan
  • F.-S. X. Yu
    Ophthalmology, Wayne State Univ/Kresge Eye Inst, Detroit, Michigan
  • Footnotes
    Commercial Relationships  K. Xu, None; F.-S.X. Yu, None.
  • Footnotes
    Support  NIH R01EY010869, R01EY017960, Research to Prevent Blindness and Midwest Eye Banks
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 5196. doi:
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      K. Xu, F.-S. X. Yu; High Glucose-Induced Gene Expression Associated with Oxidative Stress and PI3K Signaling in Diabetic Human Corneal Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5196.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : We previously demonstrated that corneal epithelial wound healing was impaired in high glucose condition and phosphatidylinositide-3-kinase (PI3K)/AKT may be specifically targeted by high glucose in corneal organ culture model. The study sought to identify gene expression related to oxidative stress in diabetic human corneal epithelial cells.

Methods: : Human corneas were obtained from the National Disease Research Interchange. Primary human corneal epithelial cells (HCECs) were collected and maintained continually in culture media containing normal glucose for non-diabetic (n=4) or high glucose (25 mM D-glucose) for diabetic patients (n=6, all type II non-insulin dependent diabetes mellitus) for three weeks and RNA was isolated. Gene expression profile of oxidative stress and antioxidant defense, PI3K-AKT signaling, and EGF/PDGF signaling in the corneal epithelial cells was determined by quantitative real time PCR array. Western blot and immunohistochemistry were used to determine levels of protein expression and cellular localization, respectively.

Results: : Real time PCR array analysis of corneal epithelial mRNA expression demonstrated dramatic increases of oxidative stress responsive genes and genes involved in reactive oxygen species metabolism, like NOS2A, CYBA, PTGS1, but down regulation of the genes related to antioxidants such as DUOX1, CYGB, SOD3 in diabetic HCECs compared with non-diabetic controls. A group of genes involved in PI3K-AKT signaling pathways were either over-expressed or under-expressed, including MAPK3, AKT, FASLG and NFKB1. High glucose impaired epidermal growth factor receptor (EGFR) signaling pathways in cultured HCECs, and more profoundly affected PI3K/AKT pathways than that of ERK by Western blotting. Immunohistological studies on diabetic human corneas showed that AKT signaling pathway was perturbed in the epithelia of diabetic corneas, but not in non-diabetic control.

Conclusions: : High glucose impairs cellular antioxidant defense and PI3K-AKT signaling in diabetic corneas and these defects may contribute to the delayed corneal epithelial wound healing in diabetic patients.

Keywords: wound healing • diabetes • cornea: epithelium 

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