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Yuki Muraoka, Hanako Ikeda, Noriko Nakano, Tomoko Hasegawa, Akira Kakizuka, Nagahisa Yoshimura; A Novel Valosin-Containing Protein Inhibitor Suppresses Photoreceptor Degeneration in a Rabbit Model of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2013;54(15):675.
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© ARVO (1962-2015); The Authors (2016-present)
Valosin-containing protein (VCP) has been shown to be involved in several pathological conditions, particularly neurodegenerative ones. Here, we investigate whether a novel VCP inhibitor can suppress photoreceptor degeneration in a rabbit model of retinitis pigmentosa (RP). Morphological and functional parameters were examined.
Twenty-three transgenic rabbits (age, 3 to 10 weeks) with rhodopsin Pro347Leu mutation were used as a model for RP. The rabbits were orally administered daily doses of either the VCP inhibitor (n = 11 rabbits, Kyoto University Substrate [KUS], 50 mg/kg/day) or a saline control solution (n = 12 rabbits). Retinal function was evaluated using scotopic full-field electroretinograms (rod b-wave amplitude, and mixed cone and rod a-wave amplitude). Morphologic changes in the visual streak photoreceptor layer were longitudinally examined with spectral domain optical coherence tomography (OCT). Vertical histological sections which passed through the center of optic disc, prepared at 10 weeks of age, were used to examine the morphology from the central retina to the mid-periphery.
Rod responses slightly increased with age in both the control and KUS groups. At 10 weeks, b-wave amplitude in the control group decreased, while it remained constant in the KUS group. Average rod b-wave amplitude in the KUS group (113.4 ± 27.7 μV) was significantly higher than in the control group (81.8 ± 36.3 μV) at 10 weeks (p = 0.006). Mixed cone and rod responses decreased with age in both groups. At 8 weeks, the average a-wave amplitude in the KUS group (76.9 ± 16.8 μV) was significantly higher than in the control group (60.8 ± 20.0 μV, p = 0.013). On OCT, the visual streak photoreceptor layer became more severely damaged with age. No difference in outer nuclear layer thickness was seen between the 2 groups at any time point examined. However, in histological sections, the length of the photoreceptor inner and outer segments was significantly longer in the KUS group (40.0 ± 0.0 μm) than in the control group (25.0 ± 4.2 μm, p = 0.037), at the area 5 mm superior to the optic disc.
These data suggested that this VCP inhibitor can morphologically and functionally suppress photoreceptor degeneration in a rabbit model of RP.
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