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Elucidation of the pathogenesis of the ocular surface diseases associated with meibomian gland lipids, commensal bacteria and sex steroid hormones

Research Project

Project/Area Number 19K09996
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56060:Ophthalmology-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Suzuki Tomo  京都府立医科大学, 医学(系)研究科(研究院), 客員講師 (30613236)

Co-Investigator(Kenkyū-buntansha) 須谷 尚史  東京大学, 定量生命科学研究所, 准教授 (30401524)
白髭 克彦  東京大学, 定量生命科学研究所, 教授 (90273854)
出来尾 格  東京慈恵会医科大学, 医学部, 講師 (80338128)
木下 茂  京都府立医科大学, 医学(系)研究科(研究院), 教授 (30116024)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsマイボーム腺 / マイボーム腺機能不全 / マイボーム腺炎 / ドライアイ / マイクロバイオーム / 脂質分析 / 性ホルモン / 加齢 / 常在細菌叢 / Cutibacterium acnes / DNAシーケンス / 眼科学 / 脂質
Outline of Research at the Start

マイボーム腺分泌脂(meibum)の網羅的脂質分析と常在細菌叢のマイクロバイオームによる網羅的解析を行い、マイボーム腺脂質代謝制御機構を解明し、さらに、マイボーム腺機能不全(MGD)患者の脂質とマイクロバイオームの分析結果から、MGDに伴う眼表面疾患(MGDに伴う蒸発亢進型ドライアイとマイボーム腺炎に関連する眼表面炎症性疾患)の病態を解明し、新規治療法の開発ストラテジーに繋げる。

Outline of Final Research Achievements

We performed comprehensive lipid analysis as well as microbiome analysis of Meibomian gland secretion(meibum) collected from the subjects incidental detailed clinical findings. The microbiome analysis showed that with aging, the bacterial flora of healthy individuals decreased in the diversity with a significant decrease in the relative abundance of Cutibacterium acnes. Lipidomic analysis showed significant decrease of the non-polar lipids (NPL) and significant increase of polar lipids (PL) in healthy elderly and patients with meibomian gland dysfunction (MGD) compared to healthy young subjects, which resulted in subjective symptoms related to the "quality" of vision (p<0.05). These results suggest that age-related changes in lipid composition and bacterial flora of the meibum may affect ocular surface homeostasis, which in turn may affect visual function.

Academic Significance and Societal Importance of the Research Achievements

加齢に伴うマイボーム腺機能の低下(MGD)は、ドライアイや眼表面炎症性疾患の発症につながるだけでなく、視機能低下等の自覚症状にも影響している。その原因となりうるmeibumの質的変化について、脂質組成と細菌叢の両面から加齢性変化を明らかにでき、今後の新規治療法の開発につながると思われる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (30 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (2 results) Journal Article (10 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 10 results,  Open Access: 7 results) Presentation (18 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Int'l Joint Research] UT Southwestern Medical Center(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] UT Southwestern Medical Center(米国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Reconsidering the pathogenesis of chalazion.2022

    • Author(s)
      Suzuki T, Katsuki N, Tsutumi R, Uchida K, Ohashi K, Eishi Y, Kinoshita S.
    • Journal Title

      Ocul Surf

      Volume: 24 Pages: 31-33

    • DOI

      10.1016/j.jtos.2021.12.010

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Alteration in meibum lipid composition and subjective symptoms due to aging and meibomian gland dysfunction.2021

    • Author(s)
      Suzuki T, Kitazawa K, Cho Y, Yoshida M, Okumura T, Sato A, Kinoshita S.
    • Journal Title

      Ocul Surf

      Volume: - Pages: 310-317

    • DOI

      10.1016/j.jtos.2021.10.003

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of aging on human meibum2021

    • Author(s)
      Butovich IA, Suzuki T.
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 62 Issue: 12 Pages: 23-23

    • DOI

      10.1167/iovs.62.12.23

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Common Features and Intra-Species Variation of Cutibacterium modestumStrains, and Emended Description of the Species.2021

    • Author(s)
      Dekio I, Okuda KI, Nishida M, Hamada-Tsutsumi S, Suzuki T, Kinoshita S, Tamura H, Ohnuma K, Murakami Y, Kinjo Y, Asahina A.
    • Journal Title

      Microorganisms

      Volume: 9 Issue: 11 Pages: 2343-2343

    • DOI

      10.3390/microorganisms9112343

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The microbiome of the meibum and ocular surface in healthy subjects.2020

    • Author(s)
      Suzuki T, Sutani T, Nakai H, Shirahige K, Kinoshita S.
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 61 Issue: 2 Pages: 18-18

    • DOI

      10.1167/iovs.61.2.18

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cutibacterium modestum sp. nov., isolated from meibum of human meibomian glands, and emended descriptions of Cutibacterium granulosum and Cutibacterium namnetense.2020

    • Author(s)
      Dekio I, Sakamoto M, Suzuki T, Yuki M, Kinoshita S, Murakami Y, Ohkuma M.
    • Journal Title

      Int J Syst Evol Microbiol

      Volume: 70 Issue: 4 Pages: 2457-2462

    • DOI

      10.1099/ijsem.0.004058

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comprehensive profiling of Asian and Caucasian meibomian gland secretions reveals similar lipidomic signatures regardless of ethnicity.2020

    • Author(s)
      Butovich IA, Suzuki T, Wojtowicz J, Bhat N, Yuksel S.
    • Journal Title

      Sci Rep

      Volume: 10 Issue: 1

    • DOI

      10.1038/s41598-020-71259-5

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Delineating a novel metabolic high triglycerides-low waxes syndrome that affects lipid homeostasis in meibomian and sebaceous glands.2020

    • Author(s)
      Butovich IA, Suzuki T.
    • Journal Title

      Exp Eye Res

      Volume: 199 Pages: 108189-108189

    • DOI

      10.1016/j.exer.2020.108189

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cyclic change of fatty acid composition in meibum during the menstrual cycle.2019

    • Author(s)
      Suzuki T, Fujiwara S, Kinoshita S, Butovich IA.
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 60 Issue: 5 Pages: 1724-1724

    • DOI

      10.1167/iovs.18-26390

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 生後2ヶ月の乳児に生じた多発霰粒腫の一例.2019

    • Author(s)
      中井浩子、杉立有弥、鈴木 智
    • Journal Title

      あたらしい眼科

      Volume: 36 Pages: 407-410

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] マイボーム腺の構造と役割2021

    • Author(s)
      鈴木 智
    • Organizer
      第44回日本眼科手術学会学術総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 霰粒腫の病態とPropionibacterium acnesの関連についての考察2021

    • Author(s)
      鈴木 智、 江石義信、内田圭介、篠宮克彦、木下 茂
    • Organizer
      角膜カンファランス2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] マイボーム腺に関連した角結膜疾患2021

    • Author(s)
      鈴木 智
    • Organizer
      第125回日本眼科学会総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] マイボーム腺炎角結膜上皮症から分離した新種Cutibacterium modestumについての考察.2021

    • Author(s)
      鈴木 智、出来尾 格、坂本光央、雪 真弘、大熊盛也、村上義之、木下 茂
    • Organizer
      フォーサム2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] 霰粒腫の病因についての考察2021

    • Author(s)
      鈴木 智, 江石義信、内田佳介、篠宮克彦、藤原 賢、木下 茂
    • Organizer
      第75回日本臨床眼科学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] マイボーム腺の構造と役割.2021

    • Author(s)
      鈴木 智
    • Organizer
      第44回日本眼科手術学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 霰粒腫の病態とPropionibacterium acnesの関連についての考察.2021

    • Author(s)
      鈴木 智、 江石義信、内田圭介、篠宮克彦、木下 茂.
    • Organizer
      角膜カンファランス2021
    • Related Report
      2020 Research-status Report
  • [Presentation] マイボーム腺常在細菌叢とmeibumの脂質組成との関連についての一考察.2020

    • Author(s)
      鈴木 智、須谷尚史、白髭克彦、中井浩子、木下茂、Igor Butovich.
    • Organizer
      第124回日本眼科学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 眼表面マイクロバイオームの加齢性変化についての検討.2020

    • Author(s)
      鈴木 智、須谷尚史、白髭克彦、木下茂.
    • Organizer
      第20回日本抗加齢医学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 特異な脂質組成を示したマイボーム腺機能不全の一症例.2020

    • Author(s)
      鈴木 智, Igor Butovich.
    • Organizer
      第74回日本臨床眼科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] マイボーム腺のマイクロバイオームの加齢性変化についての考察.2020

    • Author(s)
      鈴木 智、須谷尚史、中井浩子、白鬚克彦、木下 茂.
    • Organizer
      角膜カンファランス2020
    • Related Report
      2019 Research-status Report
  • [Presentation] 過去5年間に経験した霰粒腫206例の臨床的特徴についての考察.2020

    • Author(s)
      堤 亮太、鈴木 智、 後藤 周、川端真理子、曽田里奈、小泉 閑
    • Organizer
      角膜カンファランス2020
    • Related Report
      2019 Research-status Report
  • [Presentation] Human microbiome of eyelid skin, conjunctival sac, and meibum of the meibomian gland.2019

    • Author(s)
      Suzuki T, Sutani T, Nakai H, Shirahige K, Kinoshita S.
    • Organizer
      ARVO Annual Meeting 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Establishing the baselines for genomic and lipidomic analyses of Meibomian glands of humans and experimental animals.2019

    • Author(s)
      Butovich IA, Bhat N, Wilkerson A, McMahon A, Suzuki T, Kinoshita S, Wojtowicz JC.
    • Organizer
      ARVO Annual Meeting 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 加齢およびマイボーム腺機能不全によるマイボーム腺脂質組成の変化.2019

    • Author(s)
      鈴木 智、北澤耕司、張祐子、佐藤惇志、埴原鉱行、奥村 隆、近 亮、木下茂.
    • Organizer
      第123回日本眼科学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] マイボーム腺機能不全患者のマイボーム脂質と眼疲労との関連性.2019

    • Author(s)
      北澤耕司、張 佑子、鈴木 智、吉田雅貴、奥村 隆、近 亮、木下 茂.
    • Organizer
      第123回日本眼科学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Inflamed obstructive meibomian gland dysfunction causes ocular surface inflammation.2019

    • Author(s)
      鈴木 智.
    • Organizer
      第13回箱根ドライアイクラブ
    • Related Report
      2019 Research-status Report
  • [Presentation] マイボーム腺の月経周期に関わる生理的変化に基づくマイボーム腺機能不全への一考察.2019

    • Author(s)
      鈴木 智、藤原 賢、木下 茂.
    • Organizer
      第73回日本臨床眼科学会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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