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Masayuki Hata, Hanako Ohashi Ikeda, Munemitsu Yoshikawa, Tomoko Hasegawa, Noriko Nakano, Yuki Muraoka, Akira Kakizuka, Nagahisa Yoshimura; Neuroprotective effect of KUS121, a VCP modulator, on a rat model of ischemia and reperfusion-induced retinal degeneration.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4037. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Valosin-containing protein (VCP) is a ubiquitously expressed ATPase that is reported to be involved in several physiological activities as well as neurodegeneration. Newly synthesized compounds (Kyoto University Substances, KUSs) that inhibit VCP ATPase activity have been shown to protect cells under stress conditions. This study aimed to confirm whether KUS121, one of KUSs has a neuroprotective effect on a rat model of ischemia and reperfusion (I/R)-induced retinal degeneration.
KUS121 was orally administered to adult Thy1-GFP rats (Magill CK et al. Arch Facial Plast Surg 2010) before I/R injury. Retinal I/R injury in the rats was induced by elevating the intraocular pressure for 60 minutes with subsequent reperfusion. Spectral-domain optical coherence tomography (SD-OCT) examinations (Multiline OCT, Heidelberg Engineering) were performed to evaluate the inner retinal thickness (IR: RNFL + GCL + IPL+INL) around the optic nerve head 1, 4, and 7 days after I/R injury.
The IR thickness of untreated I/R rats (n = 9) changed from 126.6 ± 14.7 µm at baseline to 133.9 ± 9.6 µm at day 1, 96.3 ± 14.0 µm at day 4, and 84.3 ± 15.3 µm at day 7 after I/R injury. In contrast, the IR thickness of I/R rats treated with KUS121 (n = 9) changed from 125.6 ± 9.7 µm at baseline to 126.0 ± 4.8 µm at day 1, 104.7 ± 21.9 µm at day 4, and 93.0 ± 29.8 µm at day 7 after I/R injury. The mean IR thickness of the rats treated with KUS121 was greater than that of the control rats 7 days after I/R (P = 0.008).
KUS121 has a neuroprotective effect on an I/R injury rat model, suggesting the potential usefulness of the compound for the treatment of human ischemic ocular diseases.
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