2023 Fiscal Year Final Research Report
Development of Gene Therapy for Glaucoma Using Modified TrkB receptor
| Project/Area Number |
22K16985
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 56060:Ophthalmology-related
|
|---|
| Research Institution | Tokyo Metropolitan Institute of Medical Science |
|---|
Principal Investigator |
NISHIJIMA Euido 公益財団法人東京都医学総合研究所, 疾患制御研究分野, 研究員 (80909391)
|
|---|
| Project Period (FY) |
2022-04-01 – 2024-03-31
|
| Keywords | 緑内障 / 神経保護 / 視神経再生 / TrkB / AAV |
|---|
| Outline of Final Research Achievements |
This study aimed to modify TrkB, the receptor for BDNF, into a constitutively active form, creating Farnesylated intracellular TrkB (F-iTrkB), and to use this for gene therapy to recover from blindness caused by optic nerve damage. F-iTrkB was introduced into the retinas of mice using an AAV2 vector, resulting in the protection of RGCs and the promotion of axonal regeneration. 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 did reach the superior colliculus. These results suggest the possibility of partial recovery of visual function in blind mice. These findings 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、これまで治療が難しいとされてきた視神経の損傷による失明に対し、遺伝子治療という新たなアプローチで挑戦したものである。独自に開発した常時活性型TrkB分子を用いることで、損傷を受けた網膜神経細胞の保護と再生を促進することに成功した。視神経損傷マウスを用いた解析では、視神経が切断されて失明状態に陥った個体の視機能が部分的に回復することが確認され、将来的に人への応用が期待される画期的な成果と言える。今後のさらなる改良により、多くの失明患者の Quality of Life (QOL) の向上と社会復帰の実現につながることが期待される。
|
