Abstract
PurposeThe 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).MethodsEight-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.ResultsThe 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.ConclusionsTopotecan 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.
Highlights
Tissue ischemia and hypoxia may induce irreversible neuronal degeneration
These results suggested that systemic administration of topotecan inhibited increased hypoxia-inducible factor (HIF)-1α and upregulated target gene expression in post I/R retinas
This study suggested that pharmacological HIF inhibition may be possible candidates for retinal ganglion cell (RGC) degeneration induced with retinal ischemia or high intraocular pressure
Summary
Tissue ischemia and hypoxia may induce irreversible neuronal degeneration. Retinal ganglion cell (RGC) degeneration is observed accompanied with ischemia in central retinal artery occlusion and ischemic optic neuropathy. Optical coherence tomography (OCT) angiography technology reveals that capillary dropout is correlated with the decreased RGC layer thickness and visual field defects in glaucoma (Takusagawa et al, 2017). Mounting evidence suggests that retinal ischemia plays an important role in RGC degeneration (Wang et al, 2002). These damages directly affect visual acuity and visual field; therapeutic options for RGC degeneration are limited and establishment of a protective approach for RGC is desired.
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