Vision protection and axon regeneration by gene therapy of constitutive active TrkB

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07751
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: NAMEKATA Kazuhiko 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): 2020-04-01 – 2023-03-31
• Keywords: 神経再生 / TrkB / AAV / 緑内障

Outline of Final Research Achievements

In this study, we investigated the possibility of recovering visual function in blind mice by promoting the neuroprotective effect and axonal regeneration of retinal ganglion cells (RGC) by gene therapy using our originally developed constitutive active TrkB. We found that constitutive active TrkB strongly suppressed cell death induced by optic nerve crush. The regenerated axons also reached the optic chiasm. Furthermore, in glaucoma model mice, suppression of visual function decline was observed, as well as neuroprotective effect.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

これらの成果から、常時活性型TrkB分子は、細胞内のシグナル活性化を介してin vivoにおけるマウス網膜神経節細胞の保護・再生を強力に促進することが判明した。したがってアデノ随伴ウィルスなどの遺伝子治療との併用することで、緑内障などの網膜神経変性に対する新たな治療法となる可能性に期待が持たれる。