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Title: Effect of VCP modulators on gene expression profiles of retinal ganglion cells in an acute injury mouse model
Authors: Hasegawa, Tomoko
Ikeda, Hanako Ohashi
Gotoh, Norimoto
Iida, Kei  kyouindb  KAKEN_id  orcid (unconfirmed)
Iwai, Sachiko
Nakano, Noriko
Kakizuka, Akira  kyouindb  KAKEN_id
Tsujikawa, Akitaka
Author's alias: 長谷川, 智子
池田, 華子
後藤, 謙元
飯田, 慶
岩井, 祥子
垣塚, 彰
辻川, 明孝
Issue Date: 2020
Publisher: Springer Nature
Journal title: Scientific reports
Volume: 10
Issue: 1
Thesis number: 4251
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 disorders, such as glaucoma.
Rights: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
DOI(Published Version): 10.1038/s41598-020-61160-6
PubMed ID: 32144342
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