Identification and Pathophysiology of a Novel Phospholipid Metabolic Pathway Involved in Retinitis Pigmentosa

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20954
• 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: The University of Tokyo
• Principal Investigator: Ono Takashi 東京大学, 医学部附属病院, 助教 (80966010)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 網膜色素変性 / リン脂質 / コリン

Outline of Final Research Achievements

Retinitis pigmentosa is a disease in which progressive degeneration of retinal pigment epithelial cells and photoreceptors results in visual field defect. This study shows that PNPLA6, one of the genes responsible for inherited retinitis pigmentosa, has a unique phospholipase B activity that produces glycerophosphocholine via lysophosphatidylcholine in retinal pigment epithelial cells. Mice lacking PNPLA6 in the eye developed degeneration of retinal pigment epithelial cells and photoreceptor cells, indicating that phospholipid metabolism with PNPLA6 as the axis is essential for retinal homeostasis.

Free Research Field

眼科学

Academic Significance and Societal Importance of the Research Achievements

本研究は、PNPLA6が既成概念とは異なるホスホリパーゼB活性を有することに着目し、未解明だった網膜色素変性症のメカニズムを、膜リン脂質の新陳代謝機構を切り口として脂質生化学的観点から解明する独自のものである。膜リン脂質の代謝産物の補填が、網膜色素変性症の予防治療に有効である可能性がある。