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2023 Fiscal Year Final Research Report

Development of a treatment for recovery from blindness by restructuring the visual pathway

Research Project

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Project/Area Number 21K18279
Research Category

Grant-in-Aid for Challenging Research (Pioneering)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

HARADA Takayuki  公益財団法人東京都医学総合研究所, 疾患制御研究分野, 参事研究員 (90345306)

Co-Investigator(Kenkyū-buntansha) 行方 和彦  公益財団法人東京都医学総合研究所, 疾患制御研究分野, 副参事研究員 (70392355)
Project Period (FY) 2021-07-09 – 2024-03-31
Keywords視神経再生 / 視機能回復 / 緑内障
Outline of Final Research Achievements

An adeno-associated viral vector (AAV-iTrkB) was created to force expression of the intracellular region of TrkB, a high-affinity receptor for the brain-derived neurotrophic factor (BDNF), at the plasma membrane. Once the vector was administered intraocularly to the mouse model, the progression of glaucoma was suppressed. Furthermore, in an optic nerve crush model, the vector showed a strong regenerative effect that optic nerve axons reached the optic chiasm. On the other hand, in an optic tract transection model, regenerating axons successfully formed pathways to their brain targets, resulting in partial recovery of visual behavior. These results indicate that gene therapy using AAV-iTrkB vector may contribute to the inhibition of the progression of retinal degenerative diseases including glaucoma and the recovery of visual function after visual pathway injury.

Free Research Field

眼科学

Academic Significance and Societal Importance of the Research Achievements

視神経外傷や緑内障などで視神経が変性した場合、現在のところ直接的な治療法は開発されていない。今回作製した遺伝子治療ベクター (AAV-iTrkB)はBDNFの投与を必要としない画期的なものであり、視神経の保護や再生にも強力な効果を示した。この成果は国際的な専門誌において発表済み(Molecular Therapy, 2023)であり、国際特許申請も終えている。またこうした新しい手法は他の網膜・視神経変性疾患の治療にも応用可能であることから、今後も研究を継続する予定である。将来的に本研究の成果を視覚障害となっている患者に還元することができれば、大きな社会的意義を持つことが期待される。

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Published: 2025-01-30  

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