Comparison of plasticity between rod and cone visual pathways

• Project/Area Number: 16K11315
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Tohoku University
• Principal Investigator: Nishiguchi Koji 東北大学, 医学系研究科, 准教授 (30447825)
• Co-Investigator(Kenkyū-buntansha): 中澤 徹 東北大学, 医学系研究科, 教授 (30361075) ; 藤田 幸輔 東北大学, 医学系研究科, 助教 (80708115)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 遺伝子治療 / 可塑性 / 網膜 / 視覚領野 / 網膜変性 / 視覚再建 / 神経科学 / 細胞・組織 / トランスレーショナルリサーチ / 脳・神経 / ウィルス

Outline of Final Research Achievements

Mice defective of Pde6c and Gnat1 resulting in congenital lack of cone and rod function are virtually blind from birth. In this study, we treated mice of different ages by supplementing GNAT1 gene followed by assessment of visual recovery.
As a result, the levels of functional restoration measured at the retina and visual cortex were not significantly different between mice treated at 1M, 3M, and 9M following GNAT1 gene supplementation therapy. Moreover, visual restoration at the level of visual cortex were similar to mice with only Pde6c defect.
The results indicate that rod visual pathway in adult mice retain substantial plasticity.

Academic Significance and Societal Importance of the Research Achievements

近年、先天的に視覚障害をもつ網膜変性症患者に対して、遺伝子治療が試みられている。しかし、この治療では、網膜感度は改善されるが、視力は向上しない。その原因として、視覚の可塑性の欠落が考えられる。本研究では、「先天性網膜変性症に対する治療では、視覚再建に有効な感受性期が、杆体系視覚と錐体系視覚とでは異なる」との仮説を立て、その検証した。その結果、驚くべきことに、成体マウスにおいては、杆体系の視覚は非常に高い可塑性を有することが初めて明らかになった。

Research Products

• [Journal Article] Retained plsticity and substantial recovery of rod-mediated visual acuity at the visual cortex in blind adult mice with retinal dystrophy (2018)
  • Author(s): Nishiguchi KM, Fujita K, Tokashiki N, Komamura H, Takemoto-Kimura S, Okuno H, Bito H, Nakazawa T.
  • Journal Title: Mol Ther Volume: 26 Issue: 10 Pages: 2397-2406
  • DOI: 10.1016/j.ymthe.2018.07.012
  • Peer Reviewed
• [Presentation] Retained plasticity at the visual cortex and recovery of vision in blind adult mice with retinal dystrophy following gene therapy (2019)
  • Author(s): Koji M. Nishiguchi
  • Organizer: 34th Asia-Pacific Academy of Ophthalmology Congress
  • Invited
• [Presentation] Retained cortical plasticity and full recovery of rod-mediated visual acuity in blind adult mice with retinal dystrophy (2018)
  • Author(s): Koji M. Nishiguchi
  • Organizer: 6th Joint Meeting in Sendai
  • Invited
• [Presentation] Effect of timing of gene therapy to restore rod vision on the rescue effect in blind mice (2017)
  • Author(s): Koji Nishiguchi
  • Organizer: 第121回 日本眼科学会
• [Presentation] The effect of timing on visual restoration of Gnat1/Pde6c double-knockout mouse through AAV-mediated gene supplementation (2017)
  • Author(s): Koji Nishiguchi
  • Organizer: ARVO
• [Presentation] 全盲マウスに対する杆体視覚再建遺伝子治療時期によるレスキュー効果の差 (2017)
  • Author(s): 西口康二
  • Organizer: 第121回日本眼科学会総会
  • Place of Presentation: 東京（東京国際フォーラム）