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

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 R...

Full description

Saved in:
Bibliographic Details
Published in:PeerJ (San Francisco, CA) CA), 2019-10, Vol.7, p.e7849-e7849, Article e7849
Main Authors: Kunimi, Hiromitsu, Miwa, Yukihiro, Katada, Yusaku, Tsubota, Kazuo, Kurihara, Toshihide
Format: Article
Language:English
Subjects:
Analysis
Animal models
Animals
Antineoplastic agents
Cell Biology
Ganglion cysts
Gene expression
Glaucoma
Health aspects
Hypoxia
Hypoxia-inducible factor
Hypoxia-inducible factor 1a
Hypoxia-inducible factors
Ischemia
Ischemia-repufusion
Labeling
Metabolism
Molecular Biology
Neurodegeneration
Neuroprotection
Ophthalmology
Protein expression
Reperfusion
Retina
Retinal ganglion cell
Retinal ganglion cells
Topotecan
Visual evoked potentials
Visual perception
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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). 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. 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 electroretinogram and visual evoked potentials. 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.
ISSN:2167-8359
2167-8359
DOI:10.7717/peerj.7849