Study of highly sensitive OFF visual restoration gene therapy using chimeric rhodopsin

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K24053
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Keio University
• Principal Investigator: KATADA Yusaku 慶應義塾大学, 医学部(信濃町), 特任助教 (40645834)
• Project Period (FY): 2019-08-30 – 2022-03-31
• Keywords: 視覚再生 / 遺伝子治療 / 網膜色素変性

Outline of Final Research Achievements

In this study, to investigate OFF pathway regeneration, we generated mice in which the channelrhodopsin gene is expressed only in retinal ganglion cells (5B-ChR) and mice in which the channelrhodopsin gene is expressed in both retinal ganglion cells and amacrine cells (M4-ChR), induced retinal degeneration in a drug-induced manner. Then, I examined whether the OFF response could be regenerated by gene transfer of channelrhodopsin into amacrine cells.
The results showed that only ON response was obtained from 5B-ChR, as expected, but the response obtained from M4-ChR was also only ON response. On the other hand, OKR showed no regenerative effect in 5B-ChR, but only in M4-ChR.

Free Research Field

再生医療

Academic Significance and Societal Importance of the Research Achievements

スターバーストアマクリン細胞へのChRの導入によって方向性のある刺激の再生ができることが示唆された。将来系には、オプトジェネティクスを利用した視覚再生治療でアマクリン細胞へのチャネルロドプシン導入の有用性が示唆された。