2022 Fiscal Year Final Research Report
Optimizing the degenerated retinal circuitry for retinal organoid transplantation driven retinal circuitry reconstruction
| 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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| Keywords | retinal degeneration / horizontal cell / multielectrode array / retinal organoid / transplantation |
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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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| Free Research Field |
Retinal neuroscience
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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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