Gene therapy for glaucoma by stimulating neuroprotection and regeneration

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09820
• 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: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: KIMURA Atsuko 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 (60569143)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 緑内障 / TrkB / 神経保護 / AAV / RGC / 遺伝子治療

Outline of Final Research Achievements

We have made a constitutive-active TrkB molecule, which is artificially modified receptor for BDNF. Gene therapy of constitutive-active TrkB using adeno associated virus induced neuroprotection and axon regeneration in mice after optic nerve crush. However, the molecular mechanism is unknown. In this study, we have investigated gene expression pattern in RGC using RNA-seq after overexpression of constitutive-active TrkB. We found that constitutive-active TrkB changed the expression levels in many genes comparted with control. In addition, neuroprotective effect was found in hypertension glaucoma model mice by gene therapy of constitutive-active TrkB.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

F-iTrkBのウイルスベクターによる神経保護・再生の際に、変動する遺伝子群をRNA-seqによって網羅的に解析することで、細胞内におけるシグナル応答についてより深い知見を得ることができた。得られたデータを活用して、今後はより効果的な遺伝治療の開発につながることを期待したい。