advertisement

Oculus

Abstract #86364 Published in IGR 21-2

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

Hasegawa T; Ikeda HO; Gotoh N; Iida K; Iwai S; Nakano N; Kakizuka A; Tsujikawa A
Scientific reports 2020; 10: 4251


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. RESULT: antly, 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.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan.

Full article

Classification:

3.8 Pharmacology (Part of: 3 Laboratory methods)
11.8 Neuroprotection (Part of: 11 Medical treatment)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)



Issue 21-2

Change Issue


advertisement

Oculus