2017 Fiscal Year Research-status Report
変性網膜内層機能の最適化とiPSC由来網膜移植時のシナプス形成の促進に関する研究
| Project/Area Number |
17K16994
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Tu HungYa 国立研究開発法人理化学研究所, 多細胞システム形成研究センター, 訪問研究員 (10780835)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | retinal transplantation / rod bipolar cell / AII amacrine cell |
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| Outline of Annual Research Achievements |
The present study is aimed to figure out the causality between the inner retinal hyperactivity and the inactivation of upstream bipolar cell type commonly seen in retinal degeneration models. Re-activation of bipolar cells potentially resulted from suppression of the inner retinal hyperactivity is thus expected to improve the host retinal cell conditions and environments during transplantation therapy.
In contrast to the proposed work plan, the optimization of drug application for hyperactivity suppression has been conducted first in 2017, along with the setup of MEA recording/analysis and mouse iPSC-retina transplantation. In the meanwhile, the system has also been utilized for testing graft-host connection in other preparations including the xeno-transplantation case published in 2018.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The primary MEA recording method to compare the transplantation efficacy in host retinas with or without inner retinal hyperactivity has been established with qualitative and quantitative analyses. By the MEA recording, the suppression of such hyperactivity may be cooperated with preliminary results from other ongoing experiments probing the effects of host aging condition, graft composition and ambient light environment, which will even more expand the proposed aims to cover the customization and optimization of retinal transplantation therapy in future clinical treatment.
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| Strategy for Future Research Activity |
Along with the systematic comparison of retinal transplantation efficacy in different host/graft conditions, the reasons of bipolar cell inactivation and inner retinal hyperactivity are required to be specified. The therefore required mouse resource for targeted patch clamp recording has been established and secured, and candidate ion channels important for manipulating the bipolar cell state have been suggested in literature reviewing and preliminary observation. Moreover, another inhibitory cell type is now being considered as a potential target for suppressing inner retinal hyperactivity/bipolar cell inactivation.
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| Causes of Carryover |
The travel expense has been lower than expected, partially because of the generous coverage by travel grant provided by the international conference attended. However, the cost will be raised along with the enrichment of data acquirement to cover the increased participation of both domestic and international conferences expected in the following year. Also, the expected expense for conducting targeted patch clamp recording is postponed to be utilized in the following 2 years.
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