June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
A Novel Valosin-Containing Protein Inhibitor Suppresses Photoreceptor Degeneration in a Rabbit Model of Retinitis Pigmentosa
Author Affiliations & Notes
  • Yuki Muraoka
    Ophthalmology & Visual Sciences, Kyoto University, Grad Sch of Med, Kyoto, Japan
  • Hanako Ikeda
    Ophthalmology & Visual Sciences, Kyoto University, Grad Sch of Med, Kyoto, Japan
  • Noriko Nakano
    Ophthalmology & Visual Sciences, Kyoto University, Grad Sch of Med, Kyoto, Japan
  • Tomoko Hasegawa
    Ophthalmology & Visual Sciences, Kyoto University, Grad Sch of Med, Kyoto, Japan
  • Akira Kakizuka
    Laboratory of Functional Biology, Kyoto University Grad Sch of Biostudies & Solution Oriented Research for Science and Technology, Kyoto, Japan
  • Nagahisa Yoshimura
    Ophthalmology & Visual Sciences, Kyoto University, Grad Sch of Med, Kyoto, Japan
  • Footnotes
    Commercial Relationships Yuki Muraoka, None; Hanako Ikeda, Research grants from the Astellas Foundation for Research on Metabolic Disorders (F), Research grants from the Japan Foundation for Applied Enzymology (F); Noriko Nakano, PCT/JP2011/073160 (P); Tomoko Hasegawa, None; Akira Kakizuka, PCT/JP2011/073160 (P); Nagahisa Yoshimura, Canon (C), Canon (F), Nidek (C), Topcon (F), PCT/JP2011/073160 (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 675. doi:https://doi.org/
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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. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: These data suggested that this VCP inhibitor can morphologically and functionally suppress photoreceptor degeneration in a rabbit model of RP.

Keywords: 688 retina • 503 drug toxicity/drug effects • 696 retinal degenerations: hereditary  
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