Mechanism analysis of mouse bipolar cell surround response polarity reversal

Research Project

Project/Area Number	16K11333
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Ophthalmology
Research Institution	Nippon Medical School
Principal Investigator	yin chengzhu 日本医科大学, 医学部, 助教 (30535430)
Research Collaborator	kaneda makoto
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000) Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords	mouse retina / bipolar cell / NKCC1 / KCC2 / mouse / retina / 網膜双極細胞 / GABAA / GABAC / パッチクランプ法 / GABA受容体 / 電気生理学 / NKCC1、KCC2
Outline of Final Research Achievements	Surround responses of bipolar cells are explained by the hypothesis that the differences of the reversal potential of GABA-mediated chloride currents reverse the polarity between ON and OFF bipolar cells.In this study, we will investigate the distribution pattern of Cl inon transpoter in ON and OFF bipolar cells, and clarify the mechanism of surround response polarity reversal. The difference between NKCC1 and KCC2 distribution was confirmed in ON and OFF bipolar cells using electrophysiological, immunohistochemical method and fluorescence in situ hybridization method. As a result, the expression level of NKCC1 was high in ON bipolar cells, low in OFF bipolar. KCC2 showed almost the same expression level in both ON and OFF bipolar cells. rom these results, it is the intracellular Cl ion concentration that reverses the retina bipolar cell surround response polarity, and the concentration difference is caused by difference of Cl ion transpoer NKCC1 and KCC2 distribution.
Academic Significance and Societal Importance of the Research Achievements	網膜双極細胞は受容野の応答特性からON型とOFF型に分けることができる。ON型とOFF型で見られる受容野周辺部応答は同じGABA受容体を介して起こると考えられるが、どのようにして網膜双極細胞受容野周辺部応答極性を反転させているのかはまだ明らかになっていない。本研究の結果から網膜での光応答に関する重要なメカニズムが解明され、網膜での光刺激の伝達機序が一部明らかになり、視覚障害や失明などの患者さんに対する治療、人口網膜の作成などの未来眼科技術の発展に重要な理論的根拠、メカニズムを提示したと思う。