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

Description: 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.
Amount: ¥6,240,000
Funding type: research
Funder scheme: Grant-in-Aid for Challenging Research (Exploratory)
Start date: 2018-06-29
End date: 2020-03-31
Investigator: Takayuki HARADA
Institution: Tokyo Metropolitan Institute of Medical Science
Funded outputs count: 11
Funder award ID: 18K19625
OpenAlex ID: G514214591
2021 · Kentaro Hamada, Youichi Shinozaki, et al. · British Journal of Pharmacology · 9
2020 · Euido Nishijima, Kazuhiko Namekata, et al. · Scientific Reports · 17
2020 · Kazuhiko Namekata, Xiaoli Guo, et al. · Journal of Biological Chemistry · 23
2020 · Atsuko Kimura, Takahiko Noro, et al. · Neural Regeneration Research · 13
2019 · Takahiko Noro, Kazuhiko Namekata, et al. · Scientific Reports · 23
2019 · Kazuhiko Namekata, Xiaoli Guo, et al. · Journal of Biological Chemistry · 40
2019 · Kimberly Wiltrout, Alejandro Ferrer, et al. · European Journal of Human Genetics · 17
2019 · Hiroki Sano, Kazuhiko Namekata, et al. · Cell Death and Disease · 51
2018 · Chikako Harada, Atsuko Kimura, et al. · British Journal of Ophthalmology · 58
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