June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
New role of pyruvate dehydrogenase kinase 4 in retinal ganglion cell death after Ischemia/reperfusion injury
Author Affiliations & Notes
  • Ji-yeon Do
    Drug discovery and development for diabetes and metabolic disease, Kyungpook national university hospital, Daegu, Korea (the Republic of)
  • In kyu Lee
    Endocrinology, Kyungpook national university hospital, Daegu, Korea (the Republic of)
  • Dong Ho Park
    Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States
    Ophthalmology, Kyungpook national university hospital, Daegu, Korea (the Republic of)
  • Footnotes
    Commercial Relationships   Ji-yeon Do, None; In kyu Lee, None; Dong Ho Park, None
  • Footnotes
    Support  National Research Foundation of Korea (NRF), which is funded by the Ministry of Education (NRF-2014R1A1A2055007) and Korea Health Technology R&D Project of the Korea Health Industry Development Institute (KHIDI), which is funded by the Ministry of Health & Welfare, Republic of Korea (HI16C1501)
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2563. doi:
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    • Get Citation

      Ji-yeon Do, In kyu Lee, Dong Ho Park; New role of pyruvate dehydrogenase kinase 4 in retinal ganglion cell death after Ischemia/reperfusion injury. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2563.

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

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Abstract

Purpose : To determine the involvement of pyruvate dehydrogenase kinase 4 (PDK4), the regulatory enzyme in glycolytic pathway, on ischemia/reperfusion injured retinal ganglion cells (RGCs).

Methods : To induced I/R injury in C57BL/6J wild-type (WT) and PDK4 knock-out (K/O) mice, the anterior chamber of the right eye was cannulated with a 30-gauge needle connected to a saline reservoir at 150 cm above the eye, leading to a high IOP of 110 mm Hg for 1h. In Sprague-Dawley (SD) rats, retinal I/R injury was induced by elevating the IOP to 120 mm Hg for 1h. Expression of PDK4 was measured by Western blot, real-time PCR analysis. To determined the effect of PDK4 on RGC loss by I/R injury, immunofluorescence (IF) staining was performed with RGC marker at 7 days after injury.
To confirmed the effect of PDK inhibition in vitro, RGC-5 cells were changed to serum/glucose-free medium and deprived of oxygen (1 percent of oxygen) using an anaerobic chamber for 6 h with and without dichloroacetate (DCA) treatment. Western blot analysis was performed to investigate whether apoptosis protein expression regulated by DCA treatment.

Results : In WT mice and SD rat, retinal PDK4 expression was increased in I/R-injured eyes compared to uninjured eyes. I/R injury induced RGC loss and decreased thickness of retina in both WT and PDK4 K/O mice. However, in PDK4 K/O mice retina, loss of RGC were lower than those of WT. DCA, a synthetic PDK inhibitor, decreased expression of apoptosis protein induced by oxygen and glucose deprivation (OGD) in RGC-5 cells.

Conclusions : These findings suggest that PDK4 expression and activity related to RGC loss after I/R injury. Therefore, inhibition of PDK4 activity might be a therapeutic target for I/R-induced disease such as glaucoma.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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