Development of Optic Nerve Regeneration Therapy Using Adeno-Associated Vector with Active TrkB

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K20979
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Nishijima Euido 東京慈恵会医科大学, 医学部, 講師 (80909391)
• Project Period (FY): 2021-08-30 – 2024-03-31
• Keywords: 緑内障 / 神経保護 / 視神経再生 / AAV / TrkB

Outline of Final Research Achievements

In this study, the BDNF receptor TrkB was modified to create a constitutively active form, Farnesylated intracellular TrkB (F-iTrkB). When F-iTrkB was introduced into the retinas of mice using an AAV2 vector, it resulted in the protection of RGCs and the promotion of axonal regeneration. In an optic nerve injury model, the regenerated axons reached the optic chiasm but did not sufficiently reach the visual centers. However, in a model where the optic nerve was severed just before the superior colliculus, the regenerated axons successfully reached the superior colliculus. These results indicate the potential of gene therapy with F-iTrkB to partially restore visual function in blind mice. The findings of this study were published in the journal Molecular Therapy.

Free Research Field

眼科

Academic Significance and Societal Importance of the Research Achievements

本研究は、視神経および神経節細胞の障害による失明に対し、遺伝子治療を用いて解決を図ろうとした研究である。研究者らが新たに開発した常時活性型TrkB分子により、緑内障モデルマウスおよび視神経損傷マウスにおいて網膜神経細胞の保護効果が認められた。また、視神経損傷マウスを用いた実験では、視神経切断により失明した個体の視神経軸索繊維の再生が認められた。さらに、上丘付近にて視神経を切断したモデルにおいては、再生により視機能が部分的に回復することが示され、将来のヒトへの応用が期待される画期的な成果であると言える。