Nakazawa, Yosuke

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmacy 衛生化学講座 (Shiba-Kyoritsu)

Position

Associate Professor

Career 【 Display / hide

  • 2005.04
    -
    2009.03

    Faculity of pahrmacy, setsunan university, 助手

  • 2009.04
    -
    2012.03

    慶應義塾大学薬学部, 助手

  • 2012.04
    -
    2019.03

    慶應義塾大学薬学部, 助教

  • 2016.09
    -
    2017.08

    The University of Auckland, Faculty of Medical and Health Sciences, Visiting Researcher

  • 2019.04
    -
    2025.03

    Fuculty of Pharmacy, Keio University, Senior Lecturer

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Licenses and Qualifications 【 Display / hide

  • 薬剤師, 2003.04

  • 健康食品管理士, 2019.01

  • 水質管理責任者, 2025.02

 

Papers 【 Display / hide

  • TRPV1 attenuates epithelial-mesenchymal transition via calpain-protein tyrosine phosphatase pathway in lens epithelial cells

    Nakazawa Y., Nishizawa F., Kawata S., Sugiyama Y., Nagai N., Yamamoto N., Funakoshi-Tago M.

    Experimental Eye Research 258   110435 2025.09

    ISSN  00144835

     View Summary

    TRPV1, which is widely expressed throughout the body, is a non-selective cation channel activated by capsaicin. We previously reported that TRPV1 activation suppressed TGFβ2-induced epithelial-mesenchymal transition (EMT) by inhibiting Epidermal Growth Factor Receptor (EGFR) phosphorylation in lens epithelial cells (Sugiyama et al., 2021). However, the detailed molecular mechanism remains unclear. In this study, we focused on the calpain–protein tyrosine phosphatase (PTP) pathway to elucidate the detailed mechanism underlying TRPV1-induced EMT suppression. Calpain and PTP inhibitors mitigated the suppressive effect of capsaicin on TGFβ2-induced EMT in vitro and ex vivo. Finally, we shown that CalpainS1 and PTPN9 overexpression abrogated the effect of capsaicin on EMT in lens epithelial cells. Our findings indicate that calpain and PTP proteins are good candidates for preventing EMT after cataract surgery.

  • De novo <i>CDKN1C</i> variant in Beckwith-Wiedermann spectrum with atypical complications

    Moriura, Y; Nishio, Y; Ichimura, S; Noda, H; Tanahashi, Y; Yamamoto, H; Nakazawa, Y; Oso, T; Sato, Y; Takenouchi, T; Saitoh, S; Muramatsu, Y; Ogi, T

    HUMAN GENOME VARIATION 12 ( 1 ) 9 2025.05

    ISSN  2054-345X

  • Antagonistic effects of PU.1 on Gfi-1B-induced erythroid colony formation in human cord blood cells

    Manabe N., Sakurai T., Kihara-Negishi F., Nakazawa Y., Yamada T., Iwama A., Oikawa T.

    Cellular and molecular biology (Noisy-le-Grand, France) 71 ( 3 ) 48 - 56 2025.04

    ISSN  0145-5680

     View Summary

    Gfi-1B is a hematopoietic transcription factor essential for growth and differentiation of the erythroid/megakaryocytic lineages, and PU.1 is a master regulator for myeloid development. Herein, we demonstrate that PU.1 interacted with Gfi-1B in vivo by immunoprecipitation assay. GST pull-down assays showed that the binding sites were located in the Ets domain of PU.1 and the zinc finger domain of Gfi-1B. Luciferase reporter assays revealed that PU.1 and Gfi-1B antagonized each other's transcriptional activity in a dose-dependent manner. The transduction of Gfi-1B alone in human cord blood progenitor cells strongly enhanced erythroid colony formation. However, the transduction of PU.1 along with Gfi-1B in the progenitors significantly inhibited erythroid colony formation. Co-expression of Gfi-1B with a mutant PU.1, which bound to Gfi-1B but not to GATA1, another erythroid master regulator, also inhibited Gfi-1B-induced erythroid colony formation. Our results suggest that the function of Gfi-1B in the growth and differentiation of erythroid cells is antagonized by the expression of PU.1.

  • Pharmacological Behavior of Propylene Glycol/Polyvinyl Alcohol Hydrogel Incorporating Indomethacin Nanocrystals in the Skin

    Otake H., Ogata F., Nakazawa Y., Misra M., Tsubaki M., Kawasaki N., Nagai N.

    Gels 11 ( 4 )  2025.04

     View Summary

    Background: We previously reported that carbopol hydrogels incorporating indomethacin nanoparticles (IMC NPs) improved the low permeability and bioavailability of skin formulations in transdermal drug delivery systems. However, the combination of NPs with other types of hydrogels has not been sufficiently explored to date. Therefore, this study investigated propylene glycol (PG)/polyvinyl alcohol (PVA) hydrogel as an alternative base to carbopol hydrogel for incorporating IMC NPs. Methods: IMC NPs were prepared using bead milling treatment, and these NPs were incorporated into PG/PVA hydrogel (IMC-NP@PG/PVA hydrogel). The IMC concentration was measured using the HPLC method, and seven-week-old Wistar rats were used to evaluate skin absorption. Results: Bead milling reduced the IMC particle size in the PG/PVA hydrogels to the nanoscale (30–200 nm) without altering its crystalline form. The IMC-NP@PG/PVA hydrogel exhibited enhanced uniformity, solubility, and drug release compared to the IMC microparticle-loaded PG/PVA hydrogel (IMC-MP@PG/PVA hydrogel), with a 1.44-fold greater area under the concentration–time curve. Transdermal permeability studies revealed that IMC-NP@PG/PVA had 2.36-fold higher absorption than the IMC-MP@PG/PVA hydrogel, with dissolved IMC permeating the skin. Pharmacokinetics in the rats showed significantly increased plasma levels, absorption rates, and bioavailability for IMC-NP@PG/PVA, demonstrating its superior delivery efficiency. Moreover, the skin absorption of IMC-NP@PG/PVA was higher than that of carbopol hydrogel. Conclusions: These findings highlight the potential of PG/PVA hydrogels as an effective base for transdermal drug delivery systems based on NPs.

  • Changes in Protein Expression in Warmed Human Lens Epithelium Cells Using Shotgun Proteomics

    Otake H., Yamamoto T., Yamamoto N., Nakazawa Y., Miyata Y., Taga A., Sasaki H., Nagai N.

    Medicina (Lithuania) 61 ( 2 )  2025.02

    ISSN  1010660X

     View Summary

    Background and Objectives: In previous studies, we reported that the assessment of the cumulative thermal dose in the crystalline lens, conducted through computational modeling utilizing a supercomputer and the biothermal transport equation, exhibited a significant association with the incidence of nuclear cataracts. In this study, we have investigated the types of proteins that expressed underlying 35.0 °C (normal-temp) and 37.5 °C (warming-temp) by using the shotgun liquid chromatography (LC) with tandem mass spectrometry (MS/MS)-based global proteomic approach. Materials and Methods: We have discussed the changes in protein expression in warmed iHLEC-NY2 cells using Gene Ontology analysis and a label-free semiquantitative method based on spectral counting. Results: In iHLEC-NY2, 615 proteins were detected, including 307 (49.9%) present in both lenses cultured at normal-temp and warming-temp, 130 (21.1%) unique to the lens cultured at normal-temp, and 178 (29.0%) unique to the lens cultured at warming-temp. Furthermore, LC–MS/MS analysis showed that warming decreased the expression of actin, alpha cardiac muscle 1, actin-related protein 2, putative tubulin-like protein alpha-4B, ubiquitin carboxyl-terminal hydrolase 17-like protein 1, ubiquitin-ribosomal protein eL40 fusion protein, ribosome biogenesis protein BMS1 homolog, histone H2B type 1-M, and histone H2A.J. in iHLEC-NY2. Conclusions: The decreases in the specific protein levels of actin, tubulin, ubiquitin, ribosomes, and histones may be related to cataract development under warming conditions. This investigation could provide a critical framework for understanding the correlation between temperature dynamics and the development of nuclear cataracts.

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

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Reviews, Commentaries, etc. 【 Display / hide

  • 老視への対策(1) 薬物治療

    中澤 洋介

    眼科診療エクレール (中山出版)  7   293 - 296 2025.02

    Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media), Lead author, Last author, Corresponding author

  • 水晶体基礎研究の最前線

    中澤 洋介

    臨床眼科 (医学書院)  79 ( 1 ) 28 - 33 2025.01

    Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media), Lead author, Last author, Corresponding author

  • Anti-aging of the Lens

    中澤洋介

    Anti-Aging Medicine (メディカルレビュー社)  20 ( 5 ) 366 - 370 2024.10

    Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media), Lead author, Last author, Corresponding author

  • モデル動物による水晶体硬化機序と治療の可能性

    中澤 洋介

    Monthly Book Oculista (全日本病院出版会)  137   13 - 18 2024.07

    Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media), Lead author, Last author, Corresponding author

  • Role of Aquaporins and Connexins in the Lens and Contribution to Cataract Development

    Kana Aihara, Yosuke Nakazawa

    The Journal of the Japanese Society for Cataract Research (Japanese Society for Cataract Research)  36   82 - 84 2024.06

    Article, review, commentary, editorial, etc. (scientific journal), Last author, Corresponding author

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Presentations 【 Display / hide

  • Morphological Abnormalities of Lens Epithelial Cells in Mature Cataracts

    Yosuke Nakazawa

    The 129th Annual Meeting of the Japanese Ophthalmological Society , 

    2025.04

    Oral presentation (general)

  • New Developments in Presbyopia Treatment: Exploring the Potential of Pharmacotherapy

    Yosuke Nakazawa

    The 129th Annual Meeting of the Japanese Ophthalmological Society , 

    2025.04

    Symposium, workshop panel (nominated)

  • Age-related changes in elasticity of the lens cortex and nucleus in mice

    Yosuke Nakazawa

    The 129th Annual Meeting of the Japanese Ophthalmological Society , 

    2025.04

    Oral presentation (general)

  • チャネルタンパク質と疾患

    中澤洋介

    The 63st Annual Meetings of the Japanese Society for Cataract Research/ The 50th Annual Meetings of the Japanese Society for Crystallin lens Research, 

    2024.08

    Symposium, workshop panel (nominated)

  • 水晶体温度上昇による白内障進行要因の解明を目指して:ヒト由来細胞 iHLEC-NY2 の プロテオミクス解析

    門脇 玲太, 大竹 裕子, 山本 哲志, 山本 直樹, 中澤 洋介, 宮田 佳樹, 多賀 淳, 佐々木 洋, 長井 紀章

    The 63st Annual Meetings of the Japanese Society for Cataract Research/ The 50th Annual Meetings of the Japanese Society for Crystallin lens Research, 

    2024.08

    Symposium, workshop panel (nominated)

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

  • モノグルコシルヘスペリジンによるヒト老視改善効果の検証

    2025.04
    -
    2028.03

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

     View Summary

    老視は加齢に伴う水晶体硬化により調節力が減衰し、近方視が困難になる疾患である。高齢化社会に伴い、世界の老視人口は2030年にはピークの21億人に達すると推定される。老視発症抑制のためには、若年期から水晶体の弾性を低下させないことが重要である。申請者らはモノグルコシルヘスペリジン(G-Hsd)がマウスの水晶体硬化抑制作用を有することを報告している。しかし、ヒトに対する調節力減衰(老視) 抑制作用を有する食品は報告されていない。本研究では、G-Hsd 含有食品の摂取による老視抑制効果を評価するために、40歳から60歳の健常人を対象にプラセボ対照ランダム化二重盲検並行群間比較試験を実施する。

  • モニタリングとシミュレーションに基づく環境温度と老視・白内障リスクの健康影響評価

    2025.04
    -
    2028.03

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

     View Summary

    我々は眼疫学調査およびin silicoシミュレーションから核白内障リスクの52%が環境温度・深部温度上昇に伴う累積熱負荷,31%が紫外線被ばくによること,熱中症の既往が白内障発症リスクになること,サウナの習慣的利用時の水晶体温度上昇が白内障発症リスクに繋がる知見を得ている。本研究では疫学調査,臨床データとin silicoシミュレーション解析を基に,環境温度、熱中症罹患,サウナ利用による老視・白内障発症年齢の若年化と病態進行への影響を調査し予防対策にて老視や白内障発症年齢・進行を遅らせることが可能となるため,世界に先駆け超高齢社会を迎える本国で早急に開始すべき緊急性,重要性の高い課題である。

  • Analysis of the mechanism of presbyopia and development of animal models

    2023.04
    -
    2026.03

    Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

     View Summary

    本申請の目的は”①老眼発症メカニズムの解明”および“② 老視モデル動物の作成”であり、本申請研究を老眼の基礎研究の先駆け研究にする。
    本申請研究では、in vitro, ex vivoの実験系を組み合わせて遂行する。in vitro実験系はヒト水晶体上皮細胞株を用いてTRPVチャネル刺激剤で処理し、TRPVチャネルの活性・局在変化と下流シグナルを検討する。ex vivo 実験系は申請者が確立したex vivo擬老眼モデルを用いて人為的に近方視および遠方視の水晶体を再現し、TRPVチャネルの局在や活性を観察する。本申請研究遂行により、老眼発症メカニズムと老眼モデル動物創製を試みる。

  • Mechanobiological analysis of cell-basement membrane interaction during eye lens morphogenesis

    2021.04
    -
    2022.03

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

     View Summary

    眼の水晶体の主な部分は水晶体線維細胞でできており、これら細胞は水晶体嚢とよばれる強靱な繊維膜の袋の中に入っている。水晶体線維細胞は水晶体嚢の内部で秩序だった同心円層をなし球形を作っている。水晶体が光を屈折させ網膜上に焦点を結ぶ働きをするために、水晶体は正確な球状に形成される必要があるが、その形成メカニズムはよくわかっていない。本研究では水晶体線維細胞と水晶体嚢の力学的相互作用を解析することにより、水晶体の形態形成メカニズムを明らかにする。正確な球形の形成がどのようなメカニズムで制御されるのか明らかにすることは、水晶体の再生技術の開発に役立つことが期待される。
    水晶体が発生の過程でどのようなメカニズムで球状に形成されていくのか知ることは、再生医学の観点からも重要である。水晶体は主に同心円状に並ぶ水晶体線維細胞の層と、それらを包む水晶体嚢と呼ばれる基底膜から構成されている。水晶体嚢は強靱な膜であり、弾力性のある水晶体線維細胞を加圧して包んでいる可能性がある。本研究では、この水晶体嚢と水晶体線維細胞間での力学的相互作用が、どのように水晶体の球形の形成と維持に関わっているのか、マウス水晶体を用いて解析した。我々は水晶体嚢を除去し加圧を解放すると、線維細胞層は均一に拡張するのではなく、特定方向により大きく膨張することを発見した。このことから水晶体嚢による加圧は一様ではなく、水晶体の特定の領域でより強く圧力がかかっていることが示唆された。実際に原子間力顕微鏡で水晶体表面の弾性力を測定すると、領域間での違いが観察された。これらの結果から、水晶体嚢からの加圧の程度が領域により異なるために、哺乳類の水晶体は真円の球体ではなく、赤道方向の直径が前極-後極軸よりも長い押しつぶされた形(いわゆるレンズの形)になることが示唆された。よって水晶体嚢と線維細胞間の力学的相互作用により、水晶体各領域の曲率が調整されていると考えられる。さらに我々は、水晶体線維細胞の弾性力の生成に細胞膜脂質が関与していることを見いだした。今後は細胞膜脂質の合成を阻害した水晶体を用いて、それがどのように水晶体全体の形や硬さに影響するか解析していく。水晶体の硬さは、加齢による硬化が原因の老視(老眼)と深く関わっている。よって細胞膜脂質と水晶体硬化の関連を明らかにすることは、老視の治療方法の開発に向けても重要である。

  • Roles for the TRPVs channels in the lens in the initiation of presbyopia

    2020.04
    -
    2023.03

    文部科学省, Grants-in-Aid for Scientific Research, Yosuke Nakazawa, Grant-in-Aid for Scientific Research (C), Research grant, Principal investigator

     View Summary

    In this study, we examined the function of TRPV channels in the lens and contribution for presbyopia onset. We have previously reported the localization of TRPV channels in the lens, and examined the factors that influence their localization in this study. As a result, we found that the localization was changed by changes in external temperature and stimulation pressure from the ciliary muscle. We also found that administration of the anti-cataract candidate compounds hesperetin and water-soluble hesperidin suppressed the decrease in elasticity of the mouse lens due to altering the localization of TRPV channels. Furthermore, we found that Capsaicin, which is TRPV1 agonist, eye drops suppressed the development of secondary cataracts. In the future, we will examine TRPV channels in human lens samples and create the basis for the development of anti-presbyopia drugs.

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Awards 【 Display / hide

  • 日本薬学会2019年度関東支部 奨励賞

    中澤洋介, 2019.09, 公益社団法人日本薬学会関東支部, 抗白内障薬/抗老眼薬の創製を見据えて:水晶体透明性維持機構の解明と疾患予防の基盤研究

    Type of Award: Award from publisher, newspaper, foundation, etc.

  • 日本白内障学会 学術賞

    中澤洋介, 2014.09, Japanese Society for Cataract Research, 水晶体のアクアポリン0の役割および機能に関する新しい知見

  • Imaging competion Winner 2019

    2019.07, Vector Laboratories社, lens E10 section

    Type of Award: Award from publisher, newspaper, foundation, etc.

  • Highly Commended Award- Confocal microscopy

    2016.12, The University of Auckland, Mouse Lens axial sectioning image

    Country: New Zealand

  • Best Author Award - Molecular Medicine Morphology

    Nakazawa Y, Aihara K, Takeda S, Hatsusaka N, Onouchi T, Hiramatsu N, Nagata M, Nagai N, Tago-F M, Yamamoto N, Sasaki H., 2024.07, The japanese Society for clinical Molecular Morphology, Aquaporins contribute to vacuoles formation in Nile grass type II diabetic rats

    Type of Award: Honored in official journal of a scientific society, scientific journal

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Other 【 Display / hide

  • 第一回 Ocular Scientific Meeting 大会長

    2023年03月

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    1st Ocular Scientific Meeting, Chief

  • 日本薬学会 第141年会 一般シンポジウム オーガナイザー

    2021年03月

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    日本薬学会 第141年会
    一般シンポジウム オーガナイザー

    [S20] 老化と眼疾患ーいつまでも健康な視機能をー

  • 日本薬学会 第140年会 一般シンポジウム オーガナイザー

    2020年03月

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    日本薬学会 第140年会
    一般シンポジウム オーガナイザー

    今いちど,眼科領域の進歩を考える ―基礎,臨床,そしてドラッグリポジショニングについて―

  • Conference President, The 44th Annual meeting of the Japanese Society for Crystalline Lens Research.

    2018年07月

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    Conference President,
    The 44th Annual meeting of the Japanese Society for Crystalline Lens Research.

 

Courses Taught 【 Display / hide

  • STUDY OF MAJOR FIELD: (HYGIENIC CHEMISTRY)

    2025

  • SPECIAL PRACTICE IN TISSUE CULTURE AND GENE TECHNOLOGY

    2025

  • SEMINAR: (HYGIENIC CHEMISTRY)

    2025

  • RESEARCH FOR BACHELOR'S THESIS 1

    2025

  • RESEARCH APPARATUS LABORATORY COURSE

    2025

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Media Coverage 【 Display / hide

  • 増える老視、将来の薬物治療に期待

    Medical Tribune, 2022.10

Committee Experiences 【 Display / hide

  • 2018.07

    大会長, 第44回 水晶体研究会 

  • 2024.08
    -
    Present

    理事, 白内障学会

  • 2023.03

    大会長, 第一回 眼科創薬研究会 大会長

  • 2022.04
    -
    Present

    理事, 日本老視学会

  • 2022.01
    -
    Present

    監事, Ocular Scientific Meeting

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