HIF inhibitor topotecan has a neuroprotective effect in a murine retinal ischemia-reperfusion model

Hiromitsu Kunimi, Yukihiro Miwa, Yusaku Katada, Kazuo Tsubota, Toshihide Kurihara

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Purpose. The therapeutic approach for retinal ganglion cell (RGC) degeneration has not been fully established. Recently, it has been reported that hypoxia-inducible factor (HIF) may be involved with retinal neurodegeneration. In this study, we investigated neuroprotective effects of a HIF inhibitor against RGC degeneration induced in a murine model of retinal ischemia-reperfusion (I/R). Methods. Eight-weeks-old male C57/BL6J mice were treated with intraperitoneal injection of a HIF inhibitor topotecan (1.25 mg/kg) for 14 days followed by a retinal I/R procedure. Seven days after the I/R injury, the therapeutic effect was evaluated histologically and electrophysiologically. Results. The increase of HIF-1α expression and the decrease of retinal thickness and RGC number in I/R were significantly suppressed by administration of topotecan. Impaired visual function in I/R was improved by topotecan evaluated with elec-troretinogram and visual evoked potentials. Conclusions. Topotecan administration suppressed HIF-1a expression and improved RGC survival resulting in a functional protection against retinal I/R. These data indicated that the HIF inhibitor topotecan may have therapeutic potentials for RGC degeneration induced with retinal ischemia or high intraocular pressure.

Original languageEnglish
Article numbere7849
JournalPeerJ
Volume2019
Issue number10
DOIs
Publication statusPublished - 2019

Keywords

  • Hypoxia-inducible factor
  • Ischemia-repufusion
  • Neuroprotection
  • Retinal ganglion cell
  • Topotecan

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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