May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Simian Lentiviral Vector-Mediated Retinal Gene Transfer of Pigment Epithelium-Derived Factor Protects Retinal Degeneration and Electrical Defect in Royal College of Surgeons Rats
Author Affiliations & Notes
  • M. Miyazaki
    Department of Pathology, Graduate Sch Med Sci Kyushu Univ, Fukuoka, Japan
  • Y. Ikeda
    Department of Ophthalmology, Graduate Sch Med Sci Kyushu Univ, Fukuoka, Japan
  • Y. Yonemitsu
    Department of Ophthalmology, Graduate Sch Med Sci Kyushu Univ, Fukuoka, Japan
  • Y. Goto
    Clinical Neurophysiology, Graduate Sch Med Sci Kyushu Univ, Fukuoka, Japan
  • T. Sakamoto
    Department of Ophthalmology, Graduate Sch Med Sci Kagoshima Univ, Kagoshima, Japan
  • Y. Ueda
    DNAVEC Research Inc., Tsukuba-city, Ibaraki, Japan
  • M. Hasegawa
    DNAVEC Research Inc., Tsukuba-city, Ibaraki, Japan
  • S. Tobimatsu
    DNAVEC Research Inc., Tsukuba-city, Ibaraki, Japan
  • T. Ishibashi
    DNAVEC Research Inc., Tsukuba-city, Ibaraki, Japan
  • K. Sueishi
    DNAVEC Research Inc., Tsukuba-city, Ibaraki, Japan
  • Footnotes
    Commercial Relationships  M. Miyazaki, None; Y. Ikeda, None; Y. Yonemitsu, None; Y. Goto, None; T. Sakamoto, None; Y. Ueda, None; M. Hasegawa, None; S. Tobimatsu, None; T. Ishibashi, None; K. Sueishi, None.
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 3583. doi:
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      M. Miyazaki, Y. Ikeda, Y. Yonemitsu, Y. Goto, T. Sakamoto, Y. Ueda, M. Hasegawa, S. Tobimatsu, T. Ishibashi, K. Sueishi; Simian Lentiviral Vector-Mediated Retinal Gene Transfer of Pigment Epithelium-Derived Factor Protects Retinal Degeneration and Electrical Defect in Royal College of Surgeons Rats . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3583.

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

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Abstract

Abstract: : Purpose: Lentivirus vector, having a feature of long-term gene expression, is expected as an useful therapeutic method for retinal degeneration. We recently developed a novel lentivirus vector derived from the non-pathogenic simian immunodeficiency virus (SIV), and have demonstrated that SIV vector can be efficiently and safely applicable to retinal gene transfer. We assessed the effect of SIV-mediated subretinal gene transfer of pigment epithelium-derived factor (PEDF), a potent neurotrophic factor, during the disease progression in Royal College of Surgeons (RCS) rats, a well-accepted animal model of RP. Methods: Vector injection into the peripheral subretinal space of 3 weeks old RCS rats was performed. Histopathological and electroretinographic(ERG) assessment were examined at several periods. Apoptotic cells among Photoreceptor cells(PCs) were determined with TUNEL staining. Results: Histologically, PEDF gene transfer significantly protected the loss of PCs corresponding to the regions of the gene transfer compared to those of control groups until 12 weeks after gene transfer. Significant reduction of TUNEL-positive PC numbers was found in PEDF-treated eyes compared to those of the control group. A-waves of ERGs were significantly observed in the group of SIV-PEDF treated rats. Conclusions: SIV-medeated gene transfer of PEDF can protect the retinal degeneration and functional defects in RCS rats, and this effect occurs from inhibition of PC apoptosis.

Keywords: gene transfer/gene therapy • neuroprotection • retinal degenerations: hereditary 
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