A pyruvate dehydrogenase kinase inhibitor prevents retinal cell death and improves energy metabolism in rat retinas after ischemia/reperfusion injury

Kota Sato, Seiya Mochida, Daisuke Tomimoto, Takahiro Konuma, Naoki Kiyota, Satoru Tsuda, Yukihiro Shiga, Kazuko Omodaka, Toru Nakazawa

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

We aimed to assess the neuroprotective effect of a pyruvate dehydrogenase kinase (PDK) inhibitor, Nov3r after ischemia/reperfusion (IR) injury in rats. IR injury was induced by applying 150 mmHg of intraocular pressure for 50 min. Nov3r was orally administered (100 mg/kg) 3 h before and 24 h after IR injury. TUNEL-positive cells increased and immunoreactive RBPMS-positive cells decreased in the rat retinas after IR injury. Administration of Nov3r significantly ameliorated the increase in TUNEL-positive cells and prevented the RBPMS-positive cell decrease. Similarly, the number of IR-induced Iba1-positive microglial cells was significantly reduced with Nov3r treatment. Among metabolic parameters, IR damage induced the elevation of lactate and pyruvate, and the reduction of ATP. Oral administration of Nov3r ameliorated these changes. Our data suggest that the Nov3r had a retinal neuroprotective effect in IR injury in rats. This finding suggests that the regulation of pyruvate dehydrogenase (PDH) activity has potential therapeutic value by enabling metabolic reprograming in diseases associated with ischemic retinal damage, such as diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion, ischemic optic neuropathy and glaucoma.

Original languageEnglish
Article number107997
JournalExperimental Eye Research
Volume193
DOIs
Publication statusPublished - 2020 Apr

Keywords

  • ATP
  • Ischemia/reperfusion
  • Lactate
  • Microglial recruitment
  • Pyruvate
  • Pyruvate dehydrogenase
  • Pyruvate dehydrogenase kinase
  • Retina
  • Retinal ganglion cells

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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