To explore a new therapeutic approach for retinitis pigmentosa based on the patient-derived iPS cell research

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09683
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Keio University
• Principal Investigator: Ozawa Yoko 慶應義塾大学, 医学部(信濃町), 特任准教授 (90265885)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 網膜 / 網膜色素変性 / 網膜神経保護

Outline of Final Research Achievements

Retinitis pigmentosa is one of the inherited retinal disorders in which retinal photoreceptor cells and/or retinal pigment epithelium are affected, and causes blindness; the underlying mechanisms were still obscure. In the current study, we showed that the candidate drug suppressed retinal degeneration and promoted retinal protection in the mouse models of retinitis pigmentosa with rhodopsin mutation. We clarified that the drug promoted photoreceptor survival and suppressed visual dysfunction by suppressing endoplasmic reticulum stress. The result will help developing a new therapeutic approach for suppressing progression of retinitis pigmentosa.

Free Research Field

網膜

Academic Significance and Societal Importance of the Research Achievements

網膜色素変性は4000-8000人に1人という高率に生じる遺伝性疾患で国内失明原因の第2位を占める。RPE65遺伝子変異に伴う変性にのみ遺伝子治療が適応になったが、それ以外の原因遺伝子を持つ、もしくは原因遺伝子が同定されない症例に対しては治療法が無い。本研究でロドプシン変異に伴う変性のメカニズムの一端を解明し薬剤候補を示した学術的意義は大きい。更に、小胞体ストレスを来す他の変異を持つ症例にも応用しうる薬剤治療の開発につなぐ研究となった。これにより、多くの症例に適応可能な治療法の開発につながったため、社会的意義は大きい。