Ikeda, Shin-ichi



School of Medicine, Department of Ophthalmology (Shinanomachi)


Project Senior Assistant Professor (Non-tenured)/Project Assistant Professor (Non-tenured)/Project Lecturer (Non-tenured)

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Career 【 Display / hide

  • 2008.04

    Juntendo University Graduate School of Medicine, Department of Metabolism & Endocrinology, Post-doctoral fellow

  • 2014.04

    Graduate School of Medicine, The University of Tokyo, Department of Gerontological Nursing/Wound Care Management, Assistant Professor

  • 2016.04

    Keio University School of Medicine, Laboratory of Photobiology, Department of Ophthalmology, Assistant Professor

Academic Degrees 【 Display / hide

  • Ph.D., University of Tsukuba, Coursework, 2009.03


Research Areas 【 Display / hide

  • Life Science / Ophthalmology

  • Life Science / Physiology

Research Keywords 【 Display / hide

  • Extracellular Matrix

  • cell-cell-communication

  • Tissue remodeling

  • Myopia

  • skeletal muscle


Papers 【 Display / hide

  • Lipidomic analysis revealed n-3 polyunsaturated fatty acids suppressed choroidal thinning and myopia progression in mice

    Mori K, Kuroha S, Hou J, Jeong H, Ogawa M, Ikeda S.i, Kang J.X, Negishi K, Torii H, Arita M, Kurihara T, Tsubota K

    FASEB Journal (FASEB Journal)  36 ( 6 )  2022.06

    ISSN  08926638

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    Myopia is increasing worldwide and its preventable measure should urgently be pursued. N-3 polyunsaturated fatty acids (PUFAs) have been reported to have various effects such as vasodilative and anti-inflammatory, which myopia may be involved in. This study is to investigate the inhibitory effect of PUFAs on myopia progression. A lens-induced myopia (LIM) model was prepared using C57B L6/J 3-week-old mice, which were equipped with a −30 diopter lens to the right eye. Chows containing two different ratios of n-3/n-6 PUFA were administered to the mice, and myopic shifts were confirmed in choroidal thickness, refraction, and axial length in the n-3 PUFA-enriched chow group after 5 weeks. To exclude the possibility that the other ingredients in the chow may have taken the suppressive effect, fat-1 transgenic mice, which can produce n-3 PUFAs endogenously, demonstrated significant suppression of myopia. To identify what elements in n-3 PUFAs took effects on myopia suppression, enucleated eyes were used for targeted lipidomic analysis, and eicosapentaenoic acid (EPA) were characteristically distributed. Administration of EPA to the LIM model confirmed the inhibitory effect on choroidal thinning and myopia progression. Subsequently, to identify the elements and the metabolites of fatty acids effective on myopia suppression, targeted lipidomic analysis was performed and it demonstrated that metabolites of EPA were involved in myopia suppression, whereas prostaglandin E2 and 14,15-dihydrotestosterone were associated with progression of myopia. In conclusion, EPA and its metabolites are related to myopia suppression and inhibition of choroidal thinning.

  • Short-term physical inactivity induces diacylglycerol accumulation and insulin resistance in muscle via lipin1 activation

    Kakehi S, Tamura Y, Ikeda S.I, Kaga N, Taka H, Ueno N, Shiuchi T, Kubota A, Sakuraba K, Kawamori R, Watada H

    American Journal of Physiology - Endocrinology and Metabolism (American Journal of Physiology - Endocrinology and Metabolism)  321 ( 6 ) E766 - E781 2021.12

    ISSN  01931849

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    Physical inactivity impairs muscle insulin sensitivity. However, its mechanism is unclear. To model physical inactivity, we applied 24-h hind-limb cast immobilization (HCI) to mice with normal or high-fat diet (HFD) and evaluated intramyocellular lipids and the insulin signaling pathway in the soleus muscle. Although 2-wk HFD alone did not alter intramyocellular diacylglycerol (IMDG) accumulation, HCI alone increased it by 1.9-fold and HCI after HFD further increased it by 3.3-fold. Parallel to this, we found increased protein kinase C ϵ (PKCϵ) activity, reduced insulin-induced 2-deoxyglucose (2-DOG) uptake, and reduced phosphorylation of insulin receptor β (IRβ) and Akt, key molecules for insulin signaling pathway. Lipin1, which converts phosphatidic acid to diacylglycerol, showed increase of its activity by HCI, and dominant-negative lipin1 expression in muscle prevented HCI-induced IMDG accumulation and impaired insulin-induced 2-DOG uptake. Furthermore, 24-h leg cast immobilization in human increased lipin1 expression. Thus, even short-term immobilization increases IMDG and impairs insulin sensitivity in muscle via enhanced lipin1 activity.

  • Violet light suppresses lens-induced myopia via neuropsin (OPN5) in mice

    Xiaoyan Jiang, Machelle T. Pardue, Kiwako Mori, Shin-ichi Ikeda, Hidemasa Torii, Shane D’Souza, Richard A. Lang, Toshihide Kurihara, Kazuo Tsubota

    Proceedings of the National Academy of Sciences (Proceedings of the National Academy of Sciences)  118 ( 22 ) e2018840118 - e2018840118 2021.06

    ISSN  00278424

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    Myopia has become a major public health concern, particularly across much of Asia. It has been shown in multiple studies that outdoor activity has a protective effect on myopia. Recent reports have shown that short-wavelength visible violet light is the component of sunlight that appears to play an important role in preventing myopia progression in mice, chicks, and humans. The mechanism underlying this effect has not been understood. Here, we show that violet light prevents lens defocus–induced myopia in mice. This violet light effect was dependent on both time of day and retinal expression of the violet light sensitive atypical opsin, neuropsin (OPN5). These findings identify <italic>Opn5</italic>-expressing retinal ganglion cells as crucial for emmetropization in mice and suggest a strategy for myopia prevention in humans.

  • Endurance runners with intramyocellular lipid accumulation and high insulin sensitivity have enhanced expression of genes related to lipid metabolism in muscle

    Kakehi S, Tamura Y, Takeno K, Ikeda S.I, Ogura Y, Saga N, Miyatsuka T, Naito H, Kawamori R, Watada H

    Journal of Clinical Medicine (Journal of Clinical Medicine)  9 ( 12 ) 1 - 12 2020.12

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    Context: Endurance-trained athletes have high oxidative capacities, enhanced insulin sensitivities, and high intracellular lipid accumulation in muscle. These characteristics are likely due to altered gene expression levels in muscle. Design and setting: We compared intramyocellular lipid (IMCL), insulin sensitivity, and gene expression levels of the muscle in eight nonobese healthy men (control group) and seven male endurance athletes (athlete group). Their IMCL levels were measured by proton-magnetic resonance spectroscopy, and their insulin sensitivity was evaluated by glucose infusion rate (GIR) during a euglycemic–hyperinsulinemic clamp. Gene expression levels in the vastus lateralis were evaluated by quantitative RT-PCR (qRT-PCR) and microarray analysis. Results: IMCL levels in the tibialis anterior muscle were approximately 2.5 times higher in the athlete group compared to the control group, while the IMCL levels in the soleus muscle and GIR were comparable. In the microarray hierarchical clustering analysis, gene expression patterns were not clearly divided into control and athlete groups. In a gene set enrichment analysis with Gene Ontology gene sets, “RESPONSE TO LIPID” was significantly upregulated in the athlete group compared with the control group. Indeed, qRT-PCR analysis revealed that, compared to the control group, the athlete group had 2–3 times higher expressions of proliferator-activated receptor gamma coactivator-1 alpha (PGC1A), adiponectin receptors (AdipoRs), and fatty acid transporters including fatty acid transporter-1, plasma membrane-associated fatty acid binding protein, and lipoprotein lipase. Conclusions: Endurance runners with higher IMCL levels have higher expression levels of genes related to lipid metabolism such as PGC1A, AdipoRs, and fatty acid transporters in muscle.

  • Oral Bovine Milk Lactoferrin Administration Suppressed Myopia Development through Matrix Metalloproteinase 2 in a Mouse Model

    Shin-Ichi Ikeda, Toshihide Kurihara, Masataro Toda, Xiaoyan Jiang, Hidemasa Torii, Kazuo Tsubota

    Nutrients (MDPI AG)  12 ( 12 ) 1 - 9 2020.12

     View Summary

    Recent studies have reported an association between myopia development and local ocular inflammation. Lactoferrin (LF) is an iron-binding protein present in saliva, tears, and mother’s milk. Furthermore, sequestering iron by LF can cause its antibacterial property. Moreover, LF has an anti-inflammatory effect. We aimed to determine the suppressive effect of LF against the development and progress of myopia using a murine lens-induced myopia (LIM) model. We divided male C57BL/6J mice (3 weeks old) into two groups. While the experimental group was orally administered LF (1600 mg/kg/day, from 3-weeks-old to 7-weeks-old), a similar volume of Ringer’s solution was administered to the control group. We subjected the 4-week-old mice to −30 diopter lenses and no lenses on the right and left eyes, respectively. We measured the refraction and the axial length at baseline and 3 weeks after using a refractometer and a spectral domain optical coherence tomography (SD-OCT) system in both eyes. Furthermore, we determined the matrix metalloproteinase-2 (MMP-2) activity, and the amount of interleukin-6 (IL-6), MMP-2, and collagen 1A1 in the choroid or sclera. The eyes with a minus lens showed a refractive error shift and an axial length elongation in the control group, thus indicating the successful induction of myopia. However, there were no significant differences in the aforementioned parameters in the LF group. While LIM increased IL-6 expression and MMP-2 activity, it decreased collagen 1A1 content. However, orally administered LF reversed these effects. Thus, oral administration of LF suppressed lens-induced myopia development by modifying the extracellular matrix remodeling through the IL-6–MMP-2 axis in mice.

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

  • Regulatory mechanism of pathological axial elongation thorough UPR pathway

    池田真一, 池田真一, 栗原俊英, 栗原俊英, 姜効炎, 姜効炎, 森紀和子, 森紀和子, 堅田侑作, 堅田侑作, 國見洋光, 國見洋光, 三輪幸裕, 三輪幸裕, 小沢信博, 小沢信博, 伊吹麻里, 伊吹麻里, 正田千穂, 正田千穂, 鳥居秀成, 鳥居秀成, 坪田一男, 坪田一男

    日本眼科学会雑誌 125 2021

    ISSN  0029-0203

  • 東京都内小中学生における最新の近視有病率と近視関連環境因子

    四倉絵里沙, 四倉絵里沙, 鳥居秀成, 鳥居秀成, 井ノ口美香子, 井ノ口美香子, 徳村光昭, 徳村光昭, 内野美樹, 中村共生, 兵頭麻里, 森紀和子, 森紀和子, 姜効炎, 池田真一, 池田真一, 近藤眞一郎, 近藤眞一郎, 根岸一乃, 栗原俊英, 栗原俊英, 坪田一男

    日本眼光学学会総会プログラム・抄録集 56th 2020

  • マウス近視モデルにおけるクロセチンの近視抑制効果

    森紀和子, 栗原俊英, 石田文子, 姜效炎, 池田真一, 鳥居秀成, 坪田一男

    日本眼科学会雑誌 123 2019

    ISSN  0029-0203

  • バイオレットライト照射はマウス近視モデルにおける近視進行を抑制する

    姜 效炎, 栗原 俊英, 森 紀和子, 池田 真一, 汪 楊淞, 鳥居 秀成, 坪田 一男

    日本眼科学会雑誌 ((公財)日本眼科学会)  122 ( 臨増 ) 185 - 185 2018.03

    ISSN  0029-0203

  • 新規レンズ誘導マウス近視モデルの確立及び誘導レンズ屈折力依存性の検討

    姜 效炎, 栗原 俊英, 森 紀和子, 田中 康久, 池田 真一, 宮内 真紀, 四倉 絵里沙, 鳥居 秀成, 坪田 一男

    日本眼科学会雑誌 ((公財)日本眼科学会)  121 ( 臨増 ) 255 - 255 2017.03

    ISSN  0029-0203

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • Myopia development and scleral ER stress


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 池田 真一, Grant-in-Aid for Scientific Research (C), Principal investigator

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    近視進行に強膜小胞体ストレスの関与を申請者は明らかにしているが、小胞体ストレスがどのように眼軸伸長に関与するのかどうかを検証するのが2020年度の目的であった。これに対して、小胞体ストレスによって活性化されるIRE1 (Inositol Response Element 1) 、ATF6 (Activating Transcription Factor 6)、PERK (PKR-like endoplasmic reticulum kinase)の3つのセンサータンパク質から始まるUnfolding Protein Response経路の阻害剤の点眼投与を近視誘導期間中に行った。その結果、阻害剤の単剤投与ではむしろ近視を促進することがありこのことはUPR経路の抑制により他経路が代償的に活性化されて近視進行を促進したと考えられた。そこで2種混合投与試験を行ったところPERKとATF6経路の同時阻害によって近視進行が抑制され、この2経路が近視進行に関わることが示唆された。また2経路のアゴニストの点眼投与は近視進行を誘導した。またテノン嚢下に高濃度のAAVを投与することで強膜において遺伝子発現をON/OFFに方法を確立した。その方法を用いて、IRE1, PERK, ATF6をCRISPER/Cas9システムによりノックダウンするとPERKのノックダウンでは近視化が認められたのに対して、ATF6のノックダウンは近視化を抑制することが明らかとなった。ATF6阻害剤の点眼投与は非近視誘導眼においても近視が誘導された事実とATF6ノックダウン実験による近視進行抑制の事実との矛盾は今後の検討課題であるが、PERK, ATF6経路が近視進行に関与することが強く示唆される結果である。
    次年度はAAVによる強膜遺伝子制御法を用いて複数遺伝子のノックダウン実験を行う。また、近視進行に関わるATF6, PERKの標的遺伝子を見出すためin silico解析をまず行い、その後そこから得られた遺伝子の発現解析、および遺伝子の過剰発現・欠損実験を行う。

  • Effect of violet light on myopia progression


    Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), No Setting

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  • 骨格筋における免疫学的微小環境と筋機能


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 池田 真一, Grant-in-Aid for Scientific Research (B), Principal investigator

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    Quality of skeletal muscle is determined not only muscle function but also life span of individual. However, the question of what is "quality of skeletal muscle" is not answered currently. From my previous study, I hypothesized component of extracellular matrix (ECM) in basal lamina covered a skeletal muscle fiber is the substance of "quality of skeletal muscle". I compared between "good skeletal muscle" such as trained muscle and "bad skeletal muscle" such as denervated or diabetic muscle using qPCR array and identified Lamb3 gene as a muscle quality control gene. Lamb3 gene is poorly expressed in normal skeletal muscle and strongly induced during muscle hypertrophy and muscle regeneration. Lamb3 activates Akt pathway, resulting in muscle regeneration and hypertrophy. These results suggested that muscle ECM is an important internal environment and their manipulation can control muscle quality.

  • 運動による筋の質・量の変化におけるマクロファージ中心仮説


    科学研究費補助金, 池田真一, 基盤研究(C), Research grant, Principal investigator

  • 運動によるインスリン感受性亢進における筋‐マクロファージ間コミュニケーション


    科学研究費補助金, 池田真一, 若手研究(B), Research grant, Principal investigator

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