Amount of Green Fluorescent Protein in the Anterior Chamber after Intravitreal Injection of Triple-Mutated Self-Complementary AAV2 Vectors is Not Affected by Previous Vitrectomy Surgery

DOI IR Web Site PubMed 22 References
  • Takahashi Kazuhisa
    Department of Biochemistry and Molecular Biology, Nippon Medical School Department of Ophthalmology, Nippon Medical School
  • Igarashi Tsutomu
    Department of Biochemistry and Molecular Biology, Nippon Medical School Department of Ophthalmology, Nippon Medical School Department of Ophthalmology, Nippon Medical School Chiba Hokusoh Hospital
  • Miyake Koichi
    Department of Biochemistry and Molecular Biology, Nippon Medical School
  • Kobayashi Maika
    Department of Biochemistry and Molecular Biology, Nippon Medical School Department of Ophthalmology, Nippon Medical School
  • Katakai Yuko
    The Corporation for Production and Research of Laboratory Primates
  • Hayashita-Kinoh Hiromi
    Department of Biochemistry and Molecular Biology, Nippon Medical School Division of Molecular and Medical Genetics, The Institute of Medical Science, The University of Tokyo
  • Fujimoto Chiaki
    Department of Ophthalmology, Nippon Medical School
  • Kameya Shuhei
    Department of Ophthalmology, Nippon Medical School Chiba Hokusoh Hospital
  • Takahashi Hiroshi
    Department of Ophthalmology, Nippon Medical School
  • Okada Takashi
    Department of Biochemistry and Molecular Biology, Nippon Medical School Division of Molecular and Medical Genetics, The Institute of Medical Science, The University of Tokyo

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Abstract

<p>Background: The adeno-associated virus (AAV) vector is a promising vector for ocular gene therapy. Surgical internal limiting membrane peeling before AAV vector administration is useful for efficient retinal transduction. However, no report has investigated localization of AAV vectors after administration into a post-vitrectomy eye. This study investigated the effects of vitrectomy surgery on intravitreal-injected AAV vector-mediated gene expression in the anterior segment and examined the presence of neutralizing antibodies (NAbs) in serum before and after AAV vector administration. Methods: Of six eyes from three female cynomolgus monkeys, four were vitrectomized (Group VIT) and two were non-vitrectomized (Group IV). All eyes were injected with 50 μL of triple-mutated self-complementary AAV2 vector (1.9 × 1013 v.g./mL) encoding green fluorescent protein (GFP). NAbs in the serum were examined before administration and at 2 and 6 weeks after administration. GFP expression was analyzed at 19 weeks after administration. Results: Immunohistological analysis showed no GFP expression in the trabecular meshwork in any eye. The GFP genome copy in two slices of the anterior segment was 2.417 (vector genome copies/diploid genome) in Group VIT and 4.316 (vector genome copies/diploid genome) in group IV. The NAb titer was 1:15.9 (geometric mean) before administration, 1:310.7 at 2 weeks after administration, and 1:669.4 at 6 weeks after administration. Conclusion: Previous vitrectomy surgery did not affect gene expression in the anterior segment after intravitreal injection of AAV vectors.</p>

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