Multiomics approach to reveal the molecular pathogenesis of glaucoma utilizing the samples from different genetic background

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07343
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Nakano Masakazu 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (70381944)
• Co-Investigator(Kenkyū-buntansha): 田代 啓 京都府立医科大学, 医学(系)研究科(研究院), 教授 (10263097) ; 徳田 雄市 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40833661)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: マルチオミクス / 緑内障 / 人種差

Outline of Final Research Achievements

Glaucoma is the leading cause of irreversible blindness in Japan. The common variants in LOXL1 are associated with one of the subtypes of glaucoma, exfoliation glaucoma (XFG). However, the risk allele of the exonic variants in LOXL1 have been found to be inverted between Asian and Caucasian populations. Therefore, there should be other genes contributing to the disease pathogenesis.
In this study, we are establishing multiomics datasets consisting of genomic and transcriptomic data. As for the genomics, we designed a probe set to enrich the LOXL1 region from the human genome. We also performed a whole-exome association study by utilizing a next generation sequencer. As for the transcriptomics, we are collecting ocular tissues and optimized a protocol to efficiently extract RNA from the tissue. The multiomics datasets of the Japanese XFG patients should be of use to reveal molecular pathogenesis of XFG by comparing with the Caucasian datasets precisely.

Free Research Field

ゲノム医科学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

緑内障は本邦の中途失明原因の第1位であり、40才以上の有病率は5％と高く、この内の9割の症例で自覚症状が無いことが早期診断を妨げている。一方、緑内障は不可逆的に進行するものの、自覚症状のない発症早期に点眼治療を始めれば進行を抑制することが可能であり、失明に至らずに寿命を全うできる。
緑内障のバリアント情報に基づく早期検診法や発症機序解明により新規治療薬が開発できれば、医療費並びに社会福祉関連費の大幅な削減をもたらすと共に、緑内障患者の生活の質が飛躍的に向上することが予想される。