Establishment of animal models of neurodegenerative diseases and development of therapeutic strategies utilizing optogenetics

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19625
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
• Research Institution: Tokyo 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, 運動・感覚システム研究分野, 分野長 (90345306)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: Optogenetics / 緑内障 / 疾患モデル

Outline of Final Research Achievements

We previously reported that mice with deletion of the glutamate aspartate transporter (GLAST), one of the glutamate transporters, serve as a good model of normal tension glaucoma (NTG). In this project, we generated GLAST flox/flox mice. We administered light-activatable adeno-associated virus (AAV)-cre into the eye of GLAST flox/flox mice and we successfully induced GLAST deletion by light stimulation. These studies indicated that selective and partial deletion of GLAST is possible by controlling light intensity and exposure areas and time, which will lead to development of a NTG model that mimics visual field defects observed in humans. Furthermore, we reported naturally occurring NTG in non-human primates (common marmosets) and demonstrated similar pathology to human NTG.

Free Research Field

眼科学、神経科学

Academic Significance and Societal Importance of the Research Achievements

高齢化社会の到来とともに緑内障患者数はさらに増加することが予想されている。そこで適切な緑内障疾患モデルを活用した薬剤や治療法の研究が、今後ますます求められる状況にある。これまでマウスでは視野欠損部位を限局させることが困難であったが、本研究ではこの点で進歩が見られた。一方、ヒトと類似した視覚システムを持つマーモセットは、今後のトランスレーショナルリサーチにおいて極めて有用と考えられる。