September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Soluble Epoxide Hydrolase Inhibition Ameliorates Diabetic Neurotrophic Keratopathy and Accelerates Delayed Epithelial Wound Healing in the Diabetic Mouse Corneas
Author Affiliations & Notes
  • Haijing Sun
    Ophthalmology, Wayne state university, DETROIT, Michigan, United States
  • Jiaoyue Hu
    Eye Institute, Xiamen University, Xiamen, FUJIAN, China
  • Wei Li
    Eye Institute, Xiamen University, Xiamen, FUJIAN, China
  • Fushin X Yu
    Ophthalmology, Wayne state university, DETROIT, Michigan, United States
    Eye Institute, Xiamen University, Xiamen, FUJIAN, China
  • Footnotes
    Commercial Relationships   Haijing Sun, None; Jiaoyue Hu, None; Wei Li, None; Fushin Yu, None
  • Footnotes
    Support  NIH grants EY010869 and EY017960
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 1264. doi:
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      Haijing Sun, Jiaoyue Hu, Wei Li, Fushin X Yu; Soluble Epoxide Hydrolase Inhibition Ameliorates Diabetic Neurotrophic Keratopathy and Accelerates Delayed Epithelial Wound Healing in the Diabetic Mouse Corneas. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1264.

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

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Abstract

Purpose : Soluble epoxide hydrolase (encoded by Ephx2) rapidly hydrolyzes biologically active epoxyeicosatrienoic acids into the less biologically active metabolites, dihydroxyeicostrienoic acids and has been linked to cardiovascular diseases. This study was aimed to assess the adverse effects of hyperglycemia-induced expression of EPHX2 in pathogenesis of diabetic keratopathy and its reverse in EPHX2 deficient mice or by pharmacological inhibition.

Methods : C57BL/6 Ephx2 knockout mice were induced to develop diabetes by intraperitoneal injection of streptozotocin (STZ). The expression of EPHX2 detected by cDNA array was verified by immunohistochemistry. EPHX2 levels and enzymatic activities were assessed using Western blotting and sEH activity assay. The normal and diabetic mice were subjected to epithelium debridement wound and allowed to healing for indicated times. Sensory nerve regeneration post epithelium wounding was assessed with whole mount confocal microscopy.

Results : EPHX2 was only expressed in corneal epithelia of diabetic corneas and its levels increased with the duration of hyperglycemia in C57BL/6 mice. The levels of EPHX2 and sEH activities inversely correlated to the rate of epithelial wound closure. Moreover, EPHX2 inhibitor significantly accelerated epithelial wound closure in diabetic corneas. EPHX2 knockout diabetic mice have increased rate of epithelial wound closure enhanced delayed nerve regeneration, similar to the wild-type B6 mice.

Conclusions : Our data showed that EPHX2 expression increases in diabetic corneas and the elevated EPHX2 plays a detrimental role in epithelial wound repaired. Targeting EPHX2 pharmacologically may represent a new approach for treating diabetic keratopathy.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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