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Lipid profiles of retinal pigment epithelial cells and the mechanism of Drusen formation.

Research Project

Project/Area Number 19K09991
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 University

Principal Investigator

Ikeda Hanako  京都大学, 医学研究科, 特定准教授 (20372162)

Co-Investigator(Kenkyū-buntansha) 大石 明生  京都大学, 医学研究科, 特定病院助教 (50572955)
岩井 祥子  京都大学, 医学研究科, 特定研究員 (00768905)
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黄斑変性 / ドルーゼン / iPS / 網膜色素上皮 / 脂質 / 加齢黄斑変性 / iPS細胞
Outline of Research at the Start

本研究では、大きなソフトドルーゼンを多数持つAMD及びADRD患者から樹立したiPS細
胞由来のRPE細胞を用い、
1)患者・健常人iPS由来のRPE細胞内の脂質プロファイリングを解明
2)長期・ストレス負荷培養で加齢を模した状況下の脂質プロファイリングの変化を解明
3)各RPE細胞のドルーゼン形成能と脂質プロファイリングの関連を解明
し、ドルーゼンの形成メカニズム解明ならびに治療法開発の礎を築くことを目的とする。

Outline of Final Research Achievements

iPS cells were established from patients with macular degeneration and healthy subjects and induced to differentiate into retinal pigment epithelial cells. There were no significant differences in morphology or expression of retinal pigment epithelial cell-specific genes. Phagocytosis was slightly decreased in disease-derived retinal pigment epithelium. Comprehensive lipid analysis revealed that the intracellular lipid composition of retinal pigment epithelial cells derived from patients differed significantly from that of retinal pigment epithelial cells derived from healthy individuals. In addition, culture on membranes showed that patient-derived retinal pigment epithelial cells formed Drusen-like deposits.

Academic Significance and Societal Importance of the Research Achievements

現在日本において加齢黄斑変性は中途失明の原因の一つであり、患者数は増加の一途をたどっている。本研究にて、黄斑変性患者由来の網膜色素上皮細胞では、健常者由来の網膜色素上皮細胞を比較して、細胞内脂質の組成が大きく異なる事が明らかになった。詳細な検討により、ドルーゼン形成のメカニズムが詳細に解明されれば、発症予防治療法の開発につながり、学術的、また社会的な意義は非常に大きいと考えられる。

Report

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

    (21 results)

All 2022 2021 2020 2019

All Journal Article (14 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 14 results,  Open Access: 11 results) Presentation (5 results) (of which Invited: 2 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Retinal ganglion cell protection by hop-flower extract as a novel neuroprotective strategy for glaucoma2022

    • Author(s)
      Ikeda HanakoOhashi、Hasegawa Tomoko
    • Journal Title

      Neural Regeneration Research

      Volume: 17 Issue: 6 Pages: 1267-1267

    • DOI

      10.4103/1673-5374.327344

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genotype and Long-term Clinical Course of Bietti Crystalline Dystrophy in Korean and Japanese Patients.2021

    • Author(s)
      Murakami Y, Koyanagi Y, Fukushima M, Yoshimura M, Fujiwara K, Akiyama M, Momozawa Y, Ueno S, Terasaki H, Oishi A, Miyata M, Ikeda H, Tsujikawa A, Mizobuchi K, Hayashi T, Fujinami K, Tsunoda K, Park JY, Han J, Kim M, Lee CS, Kim SJ, Park TK, Joo K, Woo SJ, Ikeda Y, Sonoda KH.
    • Journal Title

      Ophthalmol Retina

      Volume: - Issue: 12 Pages: 1269-1279

    • DOI

      10.1016/j.oret.2021.02.009

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Detection Sensitivity of Retinitis Pigmentosa Progression Using Static Perimetry and Optical Coherence Tomography2021

    • Author(s)
      Hasegawa Tomoko、Oishi Akio、Ikeda Hanako Ohashi、Numa Shogo、Miyata Manabu、Otsuka Yuki、Oishi Maho、Tsujikawa Akitaka
    • Journal Title

      Translational Vision Science & Technology

      Volume: 10 Issue: 8 Pages: 31-31

    • DOI

      10.1167/tvst.10.8.31

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prediction of Trabecular Meshwork-Targeted Micro-Invasive Glaucoma Surgery Outcomes using Anterior Segment OCT Angiography2021

    • Author(s)
      Okamoto Y, Akagi T, Kameda T, Suda K, Miyake M, Ikeda HO, Numa S, Kadomoto S, Uji A, Tsujikawa A
    • Journal Title

      Sci Rep

      Volume: 11 Issue: 1 Pages: 17850-17850

    • DOI

      10.1038/s41598-021-97290-8

    • NAID

      120007144980

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Protocol for Stepwise Differentiation of Induced Pluripotent Stem Cells into Retinal Pigment Epithelium2021

    • Author(s)
      Tagawa Miho、Ikeda Hanako Ohashi、Hata Masayuki、Inoue Yumi、Iwai Sachiko、Tsujikawa Akitaka
    • Journal Title

      Methods Mol Biol

      Volume: - Pages: 307-320

    • DOI

      10.1007/7651_2021_418

    • ISBN
      9781071625842, 9781071625859
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association between topical β-blocker use and asthma attacks in glaucoma patients with asthma: a cohort study using a claims database2021

    • Author(s)
      Kido A, Miyake M, Akagi T, Ikeda HO, Kameda T, Suda K, Hasegawa T, Hiragi S, Yoshida S, Tsujikawa A, Tamura H, Kawakami K
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol

      Volume: 260 Issue: 1 Pages: 271-280

    • DOI

      10.1007/s00417-021-05357-z

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] KUS121 attenuates the progression of monosodium iodoacetate-induced osteoarthritis in rats2021

    • Author(s)
      Iwai Sachiko、Ikeda Hanako O.、Mera Hisashi、Nishitani Kohei、Saito Motoo、Tsujikawa Akitaka、Kakizuka Akira
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 15651-15651

    • DOI

      10.1038/s41598-021-95173-6

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deterioration of phagocytosis in induced pluripotent stem cell-derived retinal pigment epithelial cells established from patients with retinitis pigmentosa carrying Mer tyrosine kinase mutations2021

    • Author(s)
      Tagawa Miho、Ikeda Hanako Ohashi、Inoue Yumi、Iwai Sachiko、Iida Yuto、Hata Masayuki、Asaka Isao、Tsujikawa Akitaka
    • Journal Title

      Experimental Eye Research

      Volume: 205 Pages: 108503-108503

    • DOI

      10.1016/j.exer.2021.108503

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of VCP modulators on gene expression profiles of retinal ganglion cells in an acute injury mouse model2020

    • Author(s)
      Hasegawa Tomoko、Ikeda Hanako Ohashi、Gotoh Norimoto、Iida Kei、Iwai Sachiko、Nakano Noriko、Kakizuka Akira、Tsujikawa Akitaka
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 4251-4251

    • DOI

      10.1038/s41598-020-61160-6

    • NAID

      120006870291

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hop flower extracts mitigate retinal ganglion cell degeneration in a glaucoma mouse model2020

    • Author(s)
      Hasegawa Tomoko、Ikeda Hanako O.、Iwai Sachiko、Sasaoka Norio、Kakizuka Akira、Tsujikawa Akitaka
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 21653-21653

    • DOI

      10.1038/s41598-020-78731-2

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Safety and Effectiveness of a Novel Neuroprotectant, KUS121, in Patients With Non-Arteritic Central Retinal Artery Occlusion: An Open-Label, Non-Randomized, First-In-Humans, Phase 1/2 Trial2020

    • Author(s)
      Ikeda HO, Muraoka Y, Hata M, Sumi E, Ikeda T, Nakagawa T, Abe H, Tada H, Morita S, Kakizuka A, Yoshimura N, Tsujikawa A
    • Journal Title

      Plos ONE

      Volume: 15 Issue: 2 Pages: e0229068-e0229068

    • DOI

      10.1371/journal.pone.0229068

    • NAID

      120006799242

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nationwide incidence of central retinal artery occlusion in Japan: an exploratory descriptive study using the National Database of Health Insurance Claims (2011?2015)2020

    • Author(s)
      Kido Ai、Tamura Hiroshi、Ikeda Hanako Ohashi、Miyake Masahiro、Hiragi Shusuke、Tsujikawa Akitaka
    • Journal Title

      BMJ Open

      Volume: 10 Issue: 9 Pages: e041104-e041104

    • DOI

      10.1136/bmjopen-2020-041104

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anterior Segment Optical Coherence Tomography Angiography Imaging of Conjunctiva and Intrasclera in Treated Primary Open-Angle Glaucoma2019

    • Author(s)
      Akagi T, Uji A, Okamoto Y, Suda K, Kameda T, Nakanishi H, Ikeda HO, Miyake M, Nakano E, Motozawa N, Tsujikawa A
    • Journal Title

      Am J Ophthalmol

      Volume: 208 Pages: 313-322

    • DOI

      10.1016/j.ajo.2019.05.008

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Concentric Choriocapillaris Flow Deficits in Retinitis Pigmentosa Detected Using Wide-Angle Swept-Source Optical Coherence Tomography Angiography.2019

    • Author(s)
      Miyata M, Oishi A, Hasegawa T, Oishi M, Numa S, Otsuka Y, Uji A, Kadomoto S, Hata M, Ikeda HO, Tsujikawa A.
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 60 Issue: 4 Pages: 1044-1049

    • DOI

      10.1167/iovs.18-26176

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] PS細胞を用いたMERTKの新規遺伝子異常を有する網膜色素変性の病態解明2021

    • Author(s)
      田川 美穂, 池田 華子, 井上 由美, 岩井 祥子, 飯田 悠人, 畑 匡侑, 浅香 勲, 辻川 明孝
    • Organizer
      第125回日本眼科学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 日本・韓国におけるクリスタリン網膜症の遺伝子的・臨床的特徴2021

    • Author(s)
      村上 祐介, 小柳俊人,福島正俊,吉村茉莉花,藤原康太,秋山雅人,上野真治,寺崎浩子,大石明生,宮田学,池田 華子, 辻川 明孝,溝渕圭,他4名,池田康博,園田康平
    • Organizer
      第125回日本眼科学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 網膜色素変性の視野検査とOCT検査、眼底自発蛍光写真を用いた進行速度の検討2021

    • Author(s)
      伊賀 雄平, 長谷川 智子, 池田 華子, 宮田 学, 沼 尚吾, 大塚 悠生, 廣田 吉満, 辻川 明孝
    • Organizer
      第60回日本網膜硝子体学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 眼疾患に対する新規神経保護治療法の開発研究2021

    • Author(s)
      池田華子
    • Organizer
      京都府眼科医会夏季集談会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 眼難治性疾患に対する治療法の開発2021

    • Author(s)
      池田華子
    • Organizer
      444回 大阪眼科集談会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Patent(Industrial Property Rights)] 軟骨保護用の医薬組成物2020

    • Inventor(s)
      西谷江平、垣塚彰、池田華子ほか一、岩井祥子、斉藤元央、武蔵国弘
    • Industrial Property Rights Holder
      西谷江平、垣塚彰、池田華子ほか一、岩井祥子、斉藤元央、武蔵国弘
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] 腎臓保護用の組成物2020

    • Inventor(s)
      桑原 孝成、垣塚彰、池田華子ほか
    • Industrial Property Rights Holder
      桑原 孝成、垣塚彰、池田華子ほか
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-194628
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2025-01-30  

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