Mitochondrial dysfunction in human iPS cell-derived retinal ganglion cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16865
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Tohoku University
• Principal Investigator: Kobayashi Wataru 東北大学, 大学病院, 助教 (20646442)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 常染色体優性視神経萎縮症 / ミトコンドリア機能障害 / iPS細胞由来網膜神経節細胞

Outline of Final Research Achievements

Retinal organoids derived from normal subject and ADOA patient-derived iPS cells were cultured for up to 50 days, and retinal ganglion cells were isolated from the organoids using MACS. Comparison of cell viability by Alamar blue assay showed no significant difference between the groups. When these cells were subjected to oxidative stress with hydrogen peroxide and cell viability was compared, cell viability was significantly decreased in the ADOA group compared to the normal group. The density of neurite outgrowth in the ADOA group was significantly lower than that in the normal group.

Free Research Field

眼科学

Academic Significance and Societal Importance of the Research Achievements

本研究から常染色体優性視神経萎縮症の患者網膜では生まれつき神経線維の密度が低い可能性が示唆された。さらに高膜電位のミトコンドリアが少ないことで酸化ストレスなどの神経変性を来す障害に対して脆弱であるため早期に神経委縮を来す病態であることが考えられる。遺伝子編集により原因遺伝子を修復することで神経線維密度を改善することが出来る可能性が示唆され、今後は薬剤スクリーニングを行いこの脆弱性から保護出来るような新規薬剤の同定が出来れば視機能障害の進行を抑制できる可能性があると考えられる。