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Hanako Ikeda, Noriko Nakano, Yuki Muraoka, Masanori Hangai, Akira Kakizuka, Nagahisa Yoshimura; Neuroprotective effect of VCP inhibitors on mice models of glaucoma. Invest. Ophthalmol. Vis. Sci. 2013;54(15):419.
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© ARVO (1962-2015); The Authors (2016-present)
Valosin-containing protein (VCP) is a ubiquitously expressed ATPase that is reportedly involved in the cell cycle, membrane fusion, endoplasmic reticulum-associated degeneration etc (Nat Cell Biol, 2012. 14: 117). Newly synthesized compounds that inhibit the ATPase activity of VCP have been identified to protect cells under stress conditions. The purpose of this study was to confirm whether the compounds have a neuroprotective effect on mouse models of glaucoma.
VCP inhibitors (test) or saline (control) were orally administered to DBA/2J (a high intraocular pressure (IOP) model), GLAST knockout (KO) mice (a normal IOP model), or mice intravitreally injected with NMDA (an acute retinal ganglion cell (RGC) injury model). Spectral-domain optical coherence tomography (SD-OCT) examinations (Multiline OCT, Heidelberg Engineering) were obtained to assess cupping of the optic nerve head and evaluate the thickness of the ganglion cell complex (GCC: RNFL + GCL + IPL) around the optic nerve head. In GLAST KO and NMDA-injected mice, RGCs were counted by using scSLO images.
The GCC thickness of the control DBA/2J mice gradually decreased from 6 to 10 months. The GCC thickness of the mice treated with VCP inhibitors was greater than the control mice after the age of 7 months (P < 0.001). In control DBA/2J mice, enlargement of optic disc cupping was obvious from 8 months on. In contrast, few mice administered with VCP inhibitors showed enlargement of optic disc cupping. In GLAST KO or NMDA-injected mice, the GCC thickness of the mice treated with VCP inhibitors was greater than the control mice during the observation period. The number of remaining RGCs in the treated mice was significantly greater than those in the non-treated mice.
VCP inhibitors have a neuroprotective effect on several mouse models of glaucoma, suggesting that the compounds may provide a new treatment option for glaucoma.
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