To elucidate an enhanced function of Channelrhodopsin and its mechanism

• Project/Area Number: 18K09433
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Iwate University
• Principal Investigator: Tabata Kitako 岩手大学, 理工学部, 特任准教授 (80714576)
• Co-Investigator(Kenkyū-buntansha): 富田 浩史 岩手大学, 理工学部, 教授 (40302088) ; 菅野 江里子 岩手大学, 理工学部, 准教授 (70375210)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 眼生理学 / 遺伝子治療 / 網膜色素変性症

Outline of Final Research Achievements

Some of the green algae class family move forward to sunlight to perform photosynthesis efficiently and they use the photosensitive protein, Channelrhodopsin, to detect light. Our developed mVChR1 modified volvox-derived channelrhodopsin that has a broad range of wavelength sensitivity. The expression of mVChR1 in retinal ganglion cells may recover of blindness. Channelrhodopsin uses a vitamin A derivative, retinal, to receive light. However, there is no report how much content is in the degenerated retina. So, we compared the retinal concentration in normal retina with that in degenerated one. The retinal content in the photoreceptor degenerated retina was lower than normal one. We also investigated the synthesis pathways of retinal by using an RNA-seq analysis and revealed that up-regulations of retinal synthesis related enzyme genes were detected. These results indicated that the increase of Vitamin A possibly contributed on enhancing the mVChR1 function.

Academic Significance and Societal Importance of the Research Achievements

網膜色素変性症は4000～8000人に一人が罹患しており、重篤な場合は失明に至る。原因遺伝子は多数発見されており、未だ確立された治療法が無い。当研究室で開発したmVChR1は、視細胞変性により失明に至った網膜の神経節細胞へ発現させることにより、視力を回復させる可能性がある。mVChR1の光受容に重要な役割を担うのはレチナールであり、視細胞変性後の網膜にmVChR1を発現させると、レチナール合成関連酵素遺伝子および輸送タンパク遺伝子の一部の増加が確認されたが、レチナール量が生来のものより低いことがわかった。このことから遺伝子治療後のビタミンA投与により視機能向上できる可能性が示唆された。

Research Products

• [Journal Article] Geranylgeranyl acetone prevents glutamate-induced cell death in HT-22?cells by increasing mitochondrial membrane potential (2020)
  • Author(s): Sugano Eriko、Endo Yuka、Sugai Akihisa、Kikuchi Yuki、Tabata Kitako、Ozaki Taku、Kurose Takahiro、Takai Yoshihiro、Mitsuguchi Yoko、Honma Yoichi、Tomita Hiroshi
  • Journal Title: European Journal of Pharmacology Volume: 883 Pages: 173193-173193
  • DOI: 10.1016/j.ejphar.2020.173193
  • Peer Reviewed / Open Access
• [Journal Article] N-methyl-N-nitrosourea-induced photoreceptor degeneration is inhibited by nicotinamide via the blockade of upstream events before the phosphorylation of signaling proteins. (2019)
  • Author(s): Sugano E, Tabata K, Takezawa T, Shiraiwa R, Muraoka H, Metoki T, Kudo A, Nakazawa M, Tomita H, Iwama Y
  • Journal Title: BioMed Research International Volume: 2019 Pages: 1-10
  • DOI: 10.1155/2019/3238719
  • Peer Reviewed / Open Access
• [Journal Article] Neuroprotective effect of a dietary supplement against glutamate-induced excitotoxicity in retina (2019)
  • Author(s): Kurose T, Sugano E, Sugai A, Shiraiwa R, Kato M, Mitsuguchi Y, Takai Y, Tabata K, Honma Y, Tomita H
  • Journal Title: International Journal of Ophthalmology Volume: 12 Issue: 8 Pages: 1231-1237
  • DOI: 10.18240/ijo.2019.08.01
  • Peer Reviewed / Open Access
• [Journal Article] Natronomonas pharaonis halorhodopsin Ser81 plays a role in maintaining chloride ions near the Schiff base (2018)
  • Author(s): Sakajiri Yuko、Sugano Eriko、Watanabe Yoshito、Sakajiri Tetsuya、Tabata Kitako、Kikuchi Takeshi、Tomita Hiroshi
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 503 Issue: 4 Pages: 2326-2332
  • DOI: 10.1016/j.bbrc.2018.06.156
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Understanding of cell-cell interactions in the retina after transduction of channelrhodopsin (2020)
  • Author(s): Toshiya Kumagai, Kitako Tabata, Eriko Sugano, Hiroshi Tomita
  • Organizer: 細胞ダイバース 第3回若手ワークショップ
• [Presentation] 神経細胞の再活性化による RNA発現パターンの網羅的解析 (2020)
  • Author(s): 菅野江里子, 田端希多子, 熊谷俊哉, 冨田浩史
  • Organizer: 細胞ダイバース 公開シンポジウム
• [Presentation] 認知症モデルラットに対する保護薬の効果検討 (2019)
  • Author(s): 熊谷俊哉 田端希多子 菅野江里子 冨田浩史
  • Organizer: 日本動物学会東北支部大会
• [Presentation] Protein structural prediction of modified Volvox channelrhodopsin-1 and the verification by amino acid sequence (2018)
  • Author(s): Sugano E, Tabata K, Sakajiri Y, Watanabe Y, Tamai M, Tomita H
  • Organizer: The Association for Research in Vision and Ophthalmology
  • Int'l Joint Research
• [Presentation] Inducrion of local photoreceptor degeneration by a subretinal injection of N-Methyl-N-nitrosiurea in rats (2018)
  • Author(s): Tomita H, Sugano E, Tabata K, Yamane T, Nagasaka E, Kudo H, Yoshikawa D, Yoshikawa M, Nakazawa F, Kitaura N, Tamai M
  • Organizer: The Association for Research in Vision and Ophthalmology
  • Int'l Joint Research
• [Presentation] 光感受性遺伝子を導入した遺伝性網膜変性ラット網膜への光障害の影響 (2018)
  • Author(s): 田端希多子、菅野江里子、冨田浩史
  • Organizer: 日本眼薬理学会
• [Presentation] 網膜局所障害ラットの視機能評価 (2018)
  • Author(s): 山根峻維、田端希多子、菅野江里子、冨田浩史
  • Organizer: 日本眼薬理学会
• [Presentation] 脈絡膜メラノサイト機能の遺伝学的解析 (2018)
  • Author(s): 澁谷 仁寿, 渡邉 京祐, 奈良 篤樹, 田端 希多子, 佐藤 美穂, 前野 哲輝, 菅野 江里子, 田村 勝, 冨田 浩史, 城石 俊彦, 山本 博章
  • Organizer: 日本色素細胞学会
• [Presentation] Mitf 変異体マウスを用いた眼球における メラノサイトの遺伝学的機能解析 (2018)
  • Author(s): 澁谷 仁寿、渡邉 京祐、奈良 篤樹、田端 希多子、佐藤 美穂、前野 哲輝、菅野 江里子 、田村 勝、冨田 浩史、城石 俊彦、山本 博 章
  • Organizer: 日本遺伝学会