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Mechanism of blue light exposure-derived retinal pigment epithelium damage

Research Project

Project/Area Number 17K16964
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Ophthalmology
Research InstitutionNational Defense Medical College

Principal Investigator

Takayama Kei  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 眼科学, 講師 (10735947)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords光障害 / 酸化ストレス / 加齢黄斑変性 / 青色光 / 網膜疾患 / 糖尿病網膜症 / 網膜色素上皮 / 光照射
Outline of Final Research Achievements

We first confirmed that malondialdehyde (MDA) levels were significantly increased in eyes of age-related macular degeneration (AMD) patients. In ARPE-19 cells, MDA treatment induced vascular endothelial growth factor (VEGF) expression alternation, cell junction disruption, and autophagy dysfunction that was also observed in eyes of AMD patients. Blue light (BL) exposure increased cell death rate and ROS generation in ARPE-19 cells in a time-dependent manner; cell death was caused by apoptosis. Moreover, BL exposure induced nuclear factor (erythroid-derived)-related factor 2 (Nrf2) mRNA upregulation and Nrf2 nuclear translocation in RPE. Cell death rate was significantly higher in RPE cells from Nrf2-/- mice than from wild-type mice. Then, we compare serum levels of MDA in patients with wet wAMD, patients with dry AMD, and patients without AMD and to evaluate the efficacy of nutritional supplementation for treating elevated serum MDA in patients with wAMD

Academic Significance and Societal Importance of the Research Achievements

加齢黄斑変性(AMD)の発症に青色光が関与する。ディスプレイやLED等から青色光照射が増加し平均寿命が延びていることから、今後AMD患者が増加する可能性が高い。治療法として抗VEGF硝子体内注射や光線力学療法があるが、様々な合併症が報告されている。さらに、抗VEGF硝子体内注射・光線力学療法ともに治療費が高額である事、AMDを完治できる治療ではないために治療終了は無く延々と高額な治療費用が発生する事から、金銭面的にも患者の負担が大きい。詳細な機序の解明によって、本邦の中途失明原因4位を占めているAMDの新規発症患者を減少する事は、社会的・医療経済的に有意義な研究であると確信している。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (41 results)

All 2020 2019 2018 2017

All Journal Article (22 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 21 results,  Open Access: 18 results) Presentation (19 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Chronic chorioretinal detachment under normal intraocular pressure in eye with uveitic glaucoma after trabeculectomy: A case report.2020

    • Author(s)
      Sakurai Y, Takayama K, Abe T, Takeuchi M.
    • Journal Title

      Medicine (Baltimore).

      Volume: 99 Issue: 2 Pages: e18652-e18652

    • DOI

      10.1097/md.0000000000018652

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Outcomes of 25-Gauge Vitrectomy for Tractional and Nontractional Diabetic Macular Edema with Proliferative Diabetic Retinopathy2019

    • Author(s)
      Someya Hideaki、Takayama Kei、Takeuchi Masaru、Yokoyama Hiroshi、Kimura Takeshi、Morioka Masakazu、Takamura Yoshihiro、Sameshima Seiji、Ueda Tetsuo、Ogata Nahoko、Tashiro Maki、Kitano Shigehiko、Sakamoto Taiji
    • Journal Title

      Journal of Ophthalmology

      Volume: 2019 Pages: 1-9

    • DOI

      10.1155/2019/5304524

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comprehensive expression patterns of inflammatory cytokines in aqueous humor of patients with neovascular age-related macular degeneration2019

    • Author(s)
      Sato Tomohito、Takeuchi Masaru、Karasawa Yoko、Takayama Kei、Enoki Toshio
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 19447-19447

    • DOI

      10.1038/s41598-019-55191-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of Underlying Inflammation in Vogt?Koyanagi?Harada Disease with Sunset Glow Fundus by Multiple Analyses2019

    • Author(s)
      Murata Toshihiko、Sako Nanae、Takayama Kei、Harimoto Kozo、Kanda Koji、Herbort Carl P.、Takeuchi Masaru
    • Journal Title

      Journal of Ophthalmology

      Volume: 2019 Pages: 1-7

    • DOI

      10.1155/2019/3853794

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prognostic factors of revitrectomy for complications in eyes with proliferative diabetic retinopathy: a retrospective multicentre study2019

    • Author(s)
      Takayama Kei、Someya Hideaki、Yokoyama Hiroshi、Kimura Takeshi、Takamura Yoshihiro、Morioka Masakazu、Sameshima Seiji、Ueda Tetsuo、Ogata Nahoko、Kitano Shigehiko、Tashiro Maki、Sugimoto Masahiko、Kondo Mineo、Sakamoto Taiji、Takeuchi Masaru
    • Journal Title

      Acta Ophthalmologica

      Volume: 98 Issue: 4 Pages: 434-439

    • DOI

      10.1111/aos.14292

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Risk Factors of Neovascular Glaucoma After 25-gauge Vitrectomy for Proliferative Diabetic Retinopathy with Vitreous Hemorrhage: A Retrospective Multicenter Study2019

    • Author(s)
      Takayama K, Someya H, Yokoyama H, Takamura Y, Morioka M, Sameshima S, Ueda T, Kitano S, Tashiro M, Sugimoto M, Kondo M, Sakamoto T, Takeuchi M
    • Journal Title

      Sci Rep

      Volume: 9 Issue: 1 Pages: 14858-14858

    • DOI

      10.1038/s41598-019-51411-6

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of Acute Retinal Necrosis in a Patient with Ocular Sarcoidosis: A Case Report.2019

    • Author(s)
      Takayama K, Kaburaki T, Takeuchi M.
    • Journal Title

      Ocul Immunol Inflamm.

      Volume: 27 Issue: 7 Pages: 1067-1070

    • DOI

      10.1080/09273948.2019.1635168

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy of Adalimumab for Chronic Vogt-Koyanagi-Harada Disease Refractory to Conventional Corticosteroids and Immunosuppressive Therapy and Complicated by Central Serous Chorioretinopathy2019

    • Author(s)
      Takayama Kei、Obata Hiroto、Takeuchi Masaru
    • Journal Title

      Ocular Immunology and Inflammation

      Volume: 28 Issue: 3 Pages: 509-512

    • DOI

      10.1080/09273948.2019.1603312

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In Vitro Epiretinal Membrane Model and Antibody Permeability: Relationship With Anti-VEGF Resistance in Diabetic Macular Edema2019

    • Author(s)
      Namba R, Kaneko H, Suzumura A, Shimizu H, Kataoka K, Takayama K, Yamada K, Funahashi Y, Ito S, Nonobe N, Terasaki H
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 60 Issue: 8 Pages: 2942-2949

    • DOI

      10.1167/iovs.19-26788

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Biological Characteristics of Subsilicone Oil Fluid and Differences With Other Ocular Humors.2019

    • Author(s)
      Shimizu H, Kaneko H, Suzumura A, Takayama K, Namba R, Funahashi Y, Kataoka K, Iwase T, Hwang SJ, Ito S, Yamada K, Ueno S, Ito Y, Terasaki H.
    • Journal Title

      Transl Vis Sci Technol

      Volume: 8 Issue: 1 Pages: 28-28

    • DOI

      10.1167/tvst.8.1.28

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Silicone oil-associated retinal light exposure under a surgical microscope2018

    • Author(s)
      Yamada K, Kaneko H, Tsunekawa T, Shimizu H, Suzumura A, Namba R, Takeuchi J, Kataoka K, Takayama K, Inoue M, Ito Y, Terasaki H.
    • Journal Title

      Acta Ophthalmol.

      Volume: - Issue: 5

    • DOI

      10.1111/aos.14038

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Age-related differences in the clinical features of ocular sarcoidosis.2018

    • Author(s)
      Takayama K, Harimoto K, Sato T, Sakurai Y, Taguchi M, Kanda T, Takeuchi M.
    • Journal Title

      PLoS One

      Volume: 23 Issue: 8 Pages: e0202585-e0202585

    • DOI

      10.1371/journal.pone.0202585

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chronic postcataract endophthalmitis caused by <em>Penicillium</em> species in an immunocompetent patient2018

    • Author(s)
      Kanda Koji、Takayama Kei、Enoki Toshio、Takeuchi Masaru
    • Journal Title

      International Medical Case Reports Journal

      Volume: Volume 11 Pages: 259-262

    • DOI

      10.2147/imcrj.s175374

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel Classification of Early-stage Systemic Hypertensive Changes in Human Retina Based on OCTA Measurement of Choriocapillaris.2018

    • Author(s)
      Takayama K, Kaneko H, Ito Y, Kataoka K, Iwase T, Yasuma T, Matsuura T, Tsunekawa T, Shimizu H, Suzumura A, Ra E, Akahori T, Terasaki H.
    • Journal Title

      Sci Rep

      Volume: 8 Issue: 1 Pages: 15163-15163

    • DOI

      10.1038/s41598-018-33580-y

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Optical Coherence Tomography Angiography to Quantify Choroidal Neovascularization in Response to Aflibercept2018

    • Author(s)
      Takeuchi Jun、Kataoka Keiko、Ito Yasuki、Takayama Kei、Yasuma Tetsuhiro、Kaneko Hiroki、Terasaki Hiroko
    • Journal Title

      Ophthalmologica

      Volume: 印刷中 Issue: 2 Pages: 1-9

    • DOI

      10.1159/000487611

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Topical Corticosteroid-Resolved Rubeosis Iridis with Neovascular Glaucoma Caused by Noninfectious Granulomatous Uveitis2018

    • Author(s)
      Sora Daisuke、Takayama Kei、Taguchi Manzo、Sato Tomohito、Sakurai Yutaka、Kanda Takayuki、Takeuchi Masaru
    • Journal Title

      Case Reports in Ophthalmology

      Volume: 9 Issue: 1 Pages: 243-247

    • DOI

      10.1159/000488137

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Changes in refractive characteristics in Japanese children with Down syndrome2018

    • Author(s)
      Horio Junna、Kaneko Hiroki、Takayama Kei、Tuzuki Kinichi、Kakihara Hiroko、Iwami Miou、Kawase Yoshikatsu、Tsunekawa Taichi、Yamaguchi Naoko、Nonobe Norie、Terasaki Hiroko
    • Journal Title

      Japanese Journal of Ophthalmology

      Volume: 62 Issue: 2 Pages: 231-236

    • DOI

      10.1007/s10384-018-0565-x

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Optical Coherence Tomography Angiography of the Foveal Avascular Zone in Children With a History of Treatment-Requiring Retinopathy of Prematurity2017

    • Author(s)
      Nonobe N, Kaneko H, Ito Y, Takayama K, Kataoka K, Tsunekawa T, Matsuura T, Suzumura A, Shimizu H, Terasaki H.
    • Journal Title

      Retina

      Volume: - Issue: 1 Pages: 0-0

    • DOI

      10.1097/iae.0000000000001937

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comparison of intraocular pressure-lowering effects of ripasudil hydrochloride hydrate for inflammatory and corticosteroid-induced ocular hypertension2017

    • Author(s)
      Yasuda Mami、Takayama Kei、Kanda Takayuki、Taguchi Manzo、Someya Hideaki、Takeuchi Masaru
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 10 Pages: 0185305-0185316

    • DOI

      10.1371/journal.pone.0185305

    • Related Report
      2017 Research-status Report
    • Open Access
  • [Journal Article] Increased Retinal Thinning after Combination of Internal Limiting Membrane Peeling and Silicone Oil Endotamponade in Proliferative Diabetic Retinopathy2017

    • Author(s)
      Kaneko Hiroki、Matsuura Toshiyuki、Takayama Kei、Ito Yasuki、Iwase Takeshi、Ueno Shinji、Nonobe Norie、Yasuda Shunsuke、Kataoka Keiko、Terasaki Hiroko
    • Journal Title

      Ophthalmologica

      Volume: 238 Issue: 4 Pages: 226-235

    • DOI

      10.1159/000479482

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cytokine profiling in the sub-silicone oil fluid after vitrectomy surgeries for refractory retinal diseases2017

    • Author(s)
      Kaneko Hiroki、Takayama Kei、Asami Tetsu、Ito Yasuki、Tsunekawa Taichi、Iwase Takeshi、Funahashi Yasuhito、Ueno Shinji、Nonobe Norie、Yasuda Shunsuke、Suzumura Ayana、Shimizu Hideyuki、Kimoto Reona、Hwang Shiang-Jyi、Terasaki Hiroko
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 2640-2640

    • DOI

      10.1038/s41598-017-03124-x

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison between 1-year outcomes of aflibercept with and without photodynamic therapy for polypoidal choroidal vasculopathy: Retrospective observation study2017

    • Author(s)
      Takayama Kei、Kaneko Hiroki、Kataoka Keiko、Hattori Kyoko、Ra Eimei、Tsunekawa Taichi、Fukukita Hiroshi、Haga Fuminori、Ito Yasuki、Terasaki Hiroko
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 5 Pages: e0176100-e0176100

    • DOI

      10.1371/journal.pone.0176100

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Short-Term Outcomes of nAMD with Asteroid Hyalosis Treated by Anti-VEGF2019

    • Author(s)
      高山 圭
    • Organizer
      第123回日本眼科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Risk and Prognostic Factors of Neovascular Glaucoma After 25-gage Vitrectomy for Proliferative Diabetic Retinopathy with Vitreous Hemorrhage: A Retrospective Multicenter Study2019

    • Author(s)
      Kei Takayama
    • Organizer
      ARVO2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 夕焼け状眼底を呈したVogt-小柳-原田病でのサブクリニカルな炎症の評価方法の検討2019

    • Author(s)
      高山 圭
    • Organizer
      第53回日本眼炎症学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ベーチェット病ぶどう膜炎に対するインフリツキシマブの長期有効性の検討2019

    • Author(s)
      高山 圭
    • Organizer
      第73回日本臨床眼科学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Long-term Outcomes of Treatment with Infliximab for Behcet Uveitis2019

    • Author(s)
      Kei Takayama
    • Organizer
      第15回国際眼炎症学会
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 増殖糖尿病網膜症に合併した牽引性網膜剥離に対する極小切開硝子体手術の術後視力を予測する因子:多施設合同研究2019

    • Author(s)
      高山 圭
    • Organizer
      第58回日本網膜硝子体学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 眼サルコイドーシスの発症年齢と臨床所見の年齢による変化2019

    • Author(s)
      高山 圭
    • Organizer
      第19回日本抗加齢医学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Optical coherence tomography angiography of choriocapillaris: normative macular choriocapillaris vasculature and novel classification of early-stage systemic hypertensive changes: A cross-sectional study2018

    • Author(s)
      Takayama K
    • Organizer
      ARVO 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Difficulty of diagnosis for ocular sarcoidosis in Japanese unprecedented ageing society2018

    • Author(s)
      Takayama K
    • Organizer
      14th ISER
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 硝子体手術を施行した増殖糖尿病網膜症例の再手術となる危険因子;国内多施設共同研究2018

    • Author(s)
      高山 圭
    • Organizer
      第122回眼科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Mechanism of Light Exposure-Induced Cell Death and Cell Protection in Retinal Pigment Epithelium Cells2018

    • Author(s)
      高山 圭
    • Organizer
      第52回 日本眼炎症学会 フォーサム2018
    • Related Report
      2018 Research-status Report
  • [Presentation] 増殖糖尿病網膜に硝子体手術直前の抗VEGF硝子体投与の有無による術前術後因子の比較:多施設共同研究2018

    • Author(s)
      高山 圭
    • Organizer
      網膜硝子体学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 硝子体手術を施行した増殖糖尿病網膜症例の再手術となる危険因子 国内多施設共同研究2018

    • Author(s)
      高山 圭, 染谷 秀彬, 竹内 大, 横山 弘, 木村 剛, 高村 佳弘, 盛岡 正和, 鮫島 誠治, 坂本 泰二, 上田 哲生, 北野 滋彦, 杉本 昌彦, 近藤 峰生, J-CREST Study Group
    • Organizer
      第122回日本眼科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 難治性網膜疾患のシリコーンオイル下液のサイトカイン濃度と網膜厚の関係2018

    • Author(s)
      清水 英幸, 兼子 裕規, 高山 圭, 恒川 太一, 松浦 聡之, 鈴村 文那, 南波 里奈, 寺崎 浩子
    • Organizer
      第122回日本眼科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 空 大将, 高山 圭, 村田 敏彦, 峰 いずみ, 蕪城 俊克, 竹内 大2018

    • Author(s)
      局所ステロイド点眼が奏功した非感染性肉芽腫性ぶどう膜炎血管新生緑内障の一例
    • Organizer
      第122回日本眼科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 村田 敏彦, 高山 圭, 阿部 竜大, 神田 貴之, 播本 幸三, 竹内 大2018

    • Author(s)
      遷延型VKHの炎症の評価におけるICGスコアの有用性
    • Organizer
      第122回日本眼科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 藤田 雄己, 佐藤 智人, 染谷 秀彬, 高山 圭, 唐澤 容子, 竹内 大2018

    • Author(s)
      増殖糖尿病網膜症患者における房水中の炎症性サイトカインと房水フレア値との相関
    • Organizer
      第122回日本眼科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 高山 圭, 兼子 裕規, 松浦 聡之, 福喜多 寛, 片岡 恵子, 長坂 洋介, 恒川 太一, 伊藤 逸毅, 寺崎 浩子2017

    • Author(s)
      恒川 太一, 兼子 裕規, 高山 圭, 寺崎 浩子
    • Organizer
      第121回日本眼科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 網膜の線維化を制御する因子の探索2017

    • Author(s)
      兼子 裕規, 高山 圭, 長坂 洋介, 恒川 太一, 黄 香寂, 寺崎 浩子
    • Organizer
      第122回日本眼科学会総会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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