Effect of VCP modulators on gene expression profiles of retinal ganglion cells in an acute injury mouse model.

Scientific Reports
Tomoko HasegawaAkitaka Tsujikawa

Abstract

In glaucoma, retinal ganglion cells are damaged, leading to the progressive constriction of the visual field. We have previously shown that the valosin-containing protein (VCP) modulators, Kyoto University Substance (KUS)121 and KUS187, prevent the death of retinal ganglion cells in animal models of glaucoma, including the one generated by N-methyl-D-aspartate (NMDA)-induced neurotoxicity. KUSs appeared to avert endoplasmic reticulum (ER) stress by maintaining ATP levels, resulting in the protection of ganglion cells from cell death. To further elucidate the protective mechanisms of KUSs, we examined gene expression profiles in affected ganglion cells. We first injected KUS-treated mice with NMDA and then isolated the affected retinal ganglion cells using fluorescence-activated cell sorting. Gene expression in the cells was quantified using a next-generation sequencer. Resultantly, we found that KUS121 upregulated several genes involved in energy metabolism. In addition, we observed the upregulation of Zfp667, which has been reported to suppress apoptosis-related genes and prevent cell death. These results further support the suitability of KUS121 as a therapeutic drug in protecting retinal ganglion cells in ophthalmic disorder...Continue Reading

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Citations

Dec 12, 2020·Scientific Reports·Tomoko HasegawaAkitaka Tsujikawa

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Methods Mentioned

BETA
fluorescence-activated cell sorting
FACS
flow cytometry
PCR
RNA-Seq

Software Mentioned

R
STRIN
BZ II Analyzer
Integrated Genome Browser
TopHat2
Gene Spring14
pvclust

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis