| Project/Area Number |
20K18403
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56060:Ophthalmology-related
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| Research Institution | Osaka University |
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Principal Investigator |
Tu Hung-Ya 大阪大学, 蛋白質研究所, 助教 (10780835)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | retinal degeneration / horizontal cell / multielectrode array / retinal organoid / transplantation / organoid transplantation / bipolar cell / ribbon synapse / amacrine cell / ipRGC |
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| Outline of Research at the Start |
This study aims to facilitate the retinal reconstruction by studying the cellular mechanism potentiating host bipolar cells, the direct recipient of transplanted photoreceptors to form synapses. We have seen a functional yet inefficient visual function recovery in transplanted retinas, possibly due to the varying host bipolar cell states. It is therefore proposed to clarify the cellular interaction in the host retina that act on bipolar cell modulation. This field-crossing study will enable the multidirectional flow of knowledge and perspective among basic sciences and therapeutic innovation.
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| Outline of Final Research Achievements |
To clarify the role of horizontal cells in photoreceptor synapse reformation after retinal organoid transplantation, tamoxifen-induced conditional horizontal cell ablation model has been established in retinal degeneration mouse background. Mouse retinal organoids were transplanted to the horizontal cell-ablated degenerating retinas, and multielectrode array recording was conducted to assess the host-graft reconstruction. The host ganglion cells showed increased light responses with better signal-to-noise ratio compared to the regular transplantation preparation without horizontal cell disturbance. De novo synapses between host bipolar cells and graft photoreceptors were observed with the graft horizontal cell processes invaginated in the horizontal cell ablated retinas. These results indicate that the removal of horizontal cells from the degenerated retinas prior to transplantation facilitates the functional synapse formation between host bipolar cells and graft photoreceptors.
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| Academic Significance and Societal Importance of the Research Achievements |
我々はこれまでES/iPS細胞由来網膜組織を用いて、視細胞の変性疾患に対する移植治療の有効性を検証してきた。より良い視機能再建を目指して移植組織側の改良を行なってきたが、本研究では移植細胞を受け入る側が、より機能的に移植細胞を受け入れる環境に最適化する可能性を探るために、視細胞の神経接合に重要な水平細胞の関与について検討した。変性網膜に残存している水平細胞や移植組織中の水平細胞が移植網膜の機能的な生着に寄与するかどうかを組織学的に観察し、移植後の光に対する反応を解析することで、より移植に適した環境、及びその環境の最適化による視機能再建の可能性を提示している。
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