Kurihara, Toshihide

写真a

Affiliation

School of Medicine, Department of Ophthalmology (Shinanomachi)

Position

Associate Professor
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Profile 【 Display / hide 】

  • Toshihide Kurihara is an Associate Professor of Ophthalmology at Keio University, Tokyo, Japan. He has also been appointed as an Adjunct Assistant Professor at the Scripps Research Institute (TSRI) in La Jolla, CA, USA. He received his M.D. degree from the Faculty of Medicine, University of Tsukuba, Ibaraki, Japan, in 2001. He completed his ophthalmology residency at Keio University Hospital in 2005, and obtained his Ph.D. degree under the supervision of Professor Kazuo Tsubota from Keio University Graduate School of Medicine in 2009. Dr. Kurihara did his postdoctoral training under the mentorship of Professor Martin Friedlander at TSRI. His research interest is hypoxia responses in development, physiology, and pathophysiology of the retina. Editorial Board　Member: BioMed Research International, Journal of Ophthalmology, and Case Reports in Ophthalmological Medicine

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Career 【 Display / hide 】

  • 2001.04
    -
    2003.03

    Keio University Hospital, Department of Ophthalmology, Resident

  • 2002.07
    -
    2003.06

    National Kasumigaura Hospital, Department of Ophthalmology, Resident

  • 2003.04
    -
    2004.03

    Keio University Hospital, Department of Ophthalmology, Clinical Fellow

  • 2004.01
    -
    2005.03

    Tokyo Saiseikai Central Hospital, Ophthalmology, Clinical Fellow

  • 2005.04
    -
    2009.03

    Keio University Graduate School of Medicine, Doctoral Course

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Academic Background 【 Display / hide 】

  • 1995.04
    -
    2001.03

    University of Tsukuba, School of Medicine

    University, Graduated

  • 2005.04
    -
    2009.03

    Keio University, Graduate School of Medicine

    Graduate School, Completed

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Academic Degrees 【 Display / hide 】

  • PhD in Medicine, Keio University, Coursework, 2009.03

    Angiotensin 2 type 1 receptor signaling contributes to synaptophysin degradation and neuronal dysfunction in the diabetic retina

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Research Areas 【 Display / hide 】

  • Life Science / Ophthalmology (Ophthalmology)

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Papers 【 Display / hide 】

  • Validation of phiC31-mediated expression and functional knockout of Opn3 in the Opn3-phiC31o knock-in mouse

    Kwok RKY, Ikuta H*, Iba C*, Nakano Y*, Ma Z*, Chuai Y, Hiraoka Y, Sayanagi T, Kurihara T, Moritoh S†, Tanaka KF

    Eye Vis. (Springer Science and Business Media LLC)  12 ( 1 ) 41 2025.10

    Accepted

    　View Summary

    Abstract

    Background

    Opn3 is a non-visual blue light-sensitive opsin that has recently been reported to have an expansive repertoire of biological functions. To investigate the function of Opn3-expressing cells, we aimed to generate a system in which Opn3-expressing cells can be targeted by site-specific gene recombination.

    Methods

    Opn3-phiC31o knock-in (KI) mice were generated using the CRISPR-Cas9 method. The phiC31o-poly(A) cassette was inserted into the translation start site in exon 1. Opn3 mRNA and phiC31o mRNA were visualized by in situ hybridization (ISH). 5' rapid amplification of cDNA end (5' RACE) analysis was performed using RNAs from wild-type mouse cerebral cortex and cerebellum to identify the transcription start site of Chml, predicted to be shared with the transcription start site of Opn3. Cold-induced decrease in body temperature was monitored with a telemetric probe to confirm the phenotype of Opn3 knockout. To examine the phiC31o integrase-mediated recombination, Opn3-phiC31o mice were crossed with the ROSA26 <sup> MultiFPsΔPuro </sup> reporter and cyan fluorescent protein, mCerulean, expression was labeled by immunohistochemistry.

    Results

    The expression pattern of phiC31o mRNA was consistent with that of Opn3 mRNA in Opn3-phiC31o heterozygous mouse brains, indicating that phiC31o mRNA is expressed under the control of the Opn3 promoter. Based on the public database, the transcription start site of exon 1 of Opn3 is identical to that of Chml, suggesting that phiC31o KI disrupts Chml expression. However, Opn3-phiC31o homozygous mice sustained Chml expression, and the transcription start site of Chml was confirmed to be located 112 bp upstream of the predicted second exon. Opn3-phiC31o homozygous mice showed a larger decrease in body temperature under cold exposure compared to wild-type controls. In addition, these mice also exhibited a refractive myopia phenotype. These findings confirmed the functional knockout of Opn3. Double transgenic mice of Opn3-phiC31o and ROSA26 <sup> MultiFPsΔPuro </sup> reporter showed mCerulean expression mainly in the olfactory bulb, cerebral cortex, thalamus, and cerebellum. The recombination efficiency was 30% to 44% in the cerebellum.

    Conclusions

    Opn3-phiC31o KI mice were successfully generated. We can generate Opn3 null mice that does not disrupt Chml by preparing homozygotes of Opn3-phiC31o. We have deposited the sequences including the newly found transcription start site of Chml.

  • Diabetic Retinopathy, a Comprehensive Overview on Pathophysiology and Relevant Experimental Models

    Gettinger K, Lee D, Tomita Y, Negishi K, Kurihara T†

    Int J Mol Sci. (MDPI AG)  26 ( 20 ) 9882 - 9882 2025.10

    Last author, Corresponding author, Accepted

    　View Summary

    Diabetic retinopathy (DR) is a serious complication of diabetes, leading to vision loss worldwide. The prevalence of DR has increased in recent decades. To understand the pathophysiology of DR, various experimental models have been developed and used. In this review article, we first outline what is currently known of the general pathology of DR, including the mechanisms involved in hyperglycemia, vascular dysfunction, retinal ischemia, retinal inflammation, and retinal degeneration. We next summarize various pathologies detected in experimental models in vivo, such as in chemically and genetically induced murine, rat, and monkey models, surgical methods in larger animals like cats, and a novel murine DR model using occlusion of the carotid artery under early diabetic conditions. A general overview of the in vitro models, including cell monocultures, co-cultures, and 3D models, is also provided. This current summary enables further research to obtain a more thorough understanding of DR pathogenesis and develop appropriate treatment measures.

  • An analysis of light that reaches the eye surface in an outdoor environment

    Jiang X*, Kondo S*, Otsuka N, Kaneda D, Torii H, Negishi K, Kurihara T†, Tsubota K†

    Sci Rep. (Springer Science and Business Media LLC)  15 ( 1 ) 34319 2025.10

    Corresponding author, Accepted

    　View Summary

    The global pandemic of myopia has become an urgent public health concern in recent years. Although the mechanism remains largely unclear, the importance of outdoor light exposure on myopia prevention is widely recognized. Outdoor light is more intense and has a different spectral composition compared to indoor lighting, which are believed to contribute to the suppression of myopia. However, due to modern lifestyles, even children find it difficult to spend time outdoors. To receive outdoor light efficiently is important, yet previous reports showed inconsistent findings on optimal thresholds for outdoor light exposure. One reason may be the lack of a standardized protocol for measuring light reaching the eye surface. In this study, we developed a novel measurement device using a 3D-printed mannequin head with a light sensor probe embedded at the eye position to mimic the human eye. We assessed the proportion of light that reached the mannequin’s eye surface from different directions at various time points on a sunny day and evaluated the influence of different eyeglasses and lenses.

  • Flanged intrascleral intraocular lens fixation using 31 needles

    Nagamoto T, Kurihara T, Negishi K, Ban N†

    Retin Cases Brief Rep. (Ovid Technologies (Wolters Kluwer Health))   2025.10

    Accepted,  ISSN  1935-1089

    　View Summary

    Purpose:

    To demonstrate the novel use of a 31-gauge needle for flanged intrascleral intraocular lens (IOL) fixation using the double-needle technique.

    Methods:

    Flanged intrascleral IOL fixation was performed using the ZELOSTAT 31G (ASTI, Shizuoka, Japan) needle in a 73-year-old male with right IOL subluxation.

    Results:

    The IOL was successfully fixated with smooth intraoperative handling, excellent postoperative outcomes, no complications, and minimal refractive error.

    Conclusion:

    The 31-gauge needle has a larger inner diameter compared to the conventional 30-gauge thin-wall needle, which may facilitate intrascleral IOL fixation procedures.

  • Impact of Extended Lens-Induced Myopia on Retinal Structure and Function in Mice

    Yang Y*, Tomita Y*, Lee D, Ikeda SI, Jiang X, Negishi K, Tsubota K†, Kurihara T†

    Curr Eye Res.    doi.org/10.1080/02713683.2025.2557590 2025.09

    Last author, Corresponding author, Accepted,  ISSN  02713683

    　View Summary

    Purpose: To investigate time-dependent structural and functional retinal alterations in a mouse model of prolonged lens-induced myopia. Methods: Myopia was induced in male C57BL/6J mice by fitting −30 D lenses on both eyes starting at postnatal week 3. Mice were assigned to either a long-term induction group (3–9 weeks of age) or a short-term induction group (3–6 weeks of age). Separate groups fitted with 0 D lenses served as controls. Ocular parameters, including refraction, axial length, choroidal thickness, and retinal thickness were measured at weeks 3, 6, and 9 using an infrared photorefractor and spectral-domain optical coherence tomography. Retinal function was assessed by dark-adapted electroretinography at week 9 for the long-term group and at week 6 for the short-term group. Statistical analyses included two-way repeated-measures ANOVA followed by Bonferroni’s post hoc test for comparisons across groups and time points, and two-tailed unpaired t-test or one-way ANOVA with Fisher’s LSD post hoc test for group comparisons at individual time points. Results: After 6 weeks of myopia induction, the long-term myopia group exhibited significant reduction in refraction, axial length elongation, and choroidal thickness thinning. Inner retinal thickness was markedly reduced, and electroretinography revealed attenuated amplitudes and delayed implicit times of the oscillatory potentials. Conclusion: Prolonged lens-induced myopia in mice induces time-dependent structural and functional retinal alterations, particularly in the inner layers. This model underscores the significance of early retinal monitoring under long-term myopic conditions and serves as a platform for investigating retinal vulnerability and developing preservation strategies over time.

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

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Reviews, Commentaries, etc. 【 Display / hide 】

  • 実験近視の分子メカニズム

    栗原俊英

    新篇眼科プラクティス20 近視トータルマネジメント 生涯良好な視機能を保つために    93 - 95 2025.10

    Lead author, Last author, Corresponding author

  • 光遺伝学を用いた網膜色素変性に対する視覚再生遺伝子治療

    栗原俊英

    月刊 『視覚障害』 448   10 - 14 2025.08

    Lead author, Last author, Corresponding author

  • IRDに対する光遺伝学を用いた視覚再生治療

    栗原俊英

    Retina Medicine 14 ( 1 ) 54 - 59 2025.05

    Lead author, Last author, Corresponding author

  • 眼科分野における抗VEGF療法の変遷

    栗原俊英

    IOL&RS 39 ( 1 ) 96 - 101 2025.03

    Lead author, Last author, Corresponding author

  • 屋外へ出て近視を予防

    栗原俊英(被取材)

    秋田魁新報    12 2024.07

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Presentations 【 Display / hide 】

  • 近視進行のメカニズム

    栗原俊英

    第79回日本臨床眼科学会 ランチョンセミナー22 「解決！マイオピア」, 

    2025.10

  • 近視進行の分子メカニズムと治療ターゲット2025

    栗原俊英

    第79回日本臨床眼科学会 インストラクションコース「近視治療トータルコーディネート ～メカニズム研究、進行抑制、外科的治療～」, 

    2025.10

  • 黄斑上膜合併例におけるBRAF/MEK阻害薬投与後の漿液性網膜剥離の一例

    張琰, 富田洋平, 伴紀充, 国見洋光, 林勇海, ジャン ショウエン, 栗原俊英, 篠田肇, 根岸一乃

    第79回 日本臨床眼科学会, 

    2025.10

  • フランジ法による眼内レンズ強膜内固定術後の髄膜炎菌による眼内炎の一例

    永本崇, 伴紀充, 利根川直也, 姜效炎, 國見洋光, 富田洋平, 栗原俊英, 篠田肇, 根岸一乃

    第79回日本臨床眼科学会, 

    2025.10

  • 我が国における新型コロナウイルス感染症(COVID-19)流行後の眼科手術件数の回復状況

    伴紀充, 永本崇, 利根川直也, 栗原俊英, 根岸一乃, 福津佳苗, 石田晋, 寺尾亮, 相原一, 太田光, 石川桂二郎, 園田康平

    第79回日本臨床眼科学会, 

    2025.10

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

  • Establishment of therapeutic intervention methods for fibrotic scar formation in age-related macular degeneration through hypoxia response control

    2024.04
    -
    2027.03

    基盤研究(C), Principal investigator

  • 非視覚型光受容体による光マルチセンシング機構の解明と光新規治療法開発

    2022.10
    -
    2028.03

    国立研究開発法人日本医療研究開発機構(AMED), 令和4年度 「革新的先端研究開発支援事業（AMED-CREST）」, No Setting

  • 低酸素応答制御機能を持つ静岡県産魚類由来成分の探索と疾患制御に関する研究

    2022.08
    -
    2025.03

    静岡県, マリンバイオテクノロジーを核としたシーズ創出研究業務委託 ￥286,800,000-, No Setting

  • 低酸素応答を標的とした予防から治療までを網羅する網膜疾患制御技術開発

    2018.04
    -
    2021.03

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

  • Approach for retinal diseases based on regulation of hypoxia response

    2015.04
    -
    2018.03

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

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Intellectual Property Rights, etc. 【 Display / hide 】

  • α１ブロッカーを含む近視進行抑制用点眼剤

    Date applied： 特願2024-519839  2022.08 

    Date published： WO2024/048750  2024.03 

    Date issued： 特許第7640163号  2025.03

    Date registered： 2025.02

    Patent

  • ＨＩＦ抑制用組成物

    Date applied： 特願2021-504090  2020.03 

    Date issued： 特許第7598591号  2024.12

    Date registered： 2024.12

    Patent

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Awards 【 Display / hide 】

  • 第46回日本光医学・光生物学会学術奨励賞（医学領域）

    栗原俊英, 2024.07, 日本光医学・光生物学会, 非視覚光受容による近視進行抑制に関わる脳内回路の探索

  • 日本眼科学会評議員会賞

    栗原俊英, 2024.04, 日本眼科学会, 光生物学を基盤とした眼疾患病態生理の理解と治療開発

  • 第62回日本網膜硝子体学会総会優秀演題

    Ayaka Naka, Deokho Lee, Yan Zhang, Chiho Shoda, Satoshi Imanishi, Hiroyuki Nakashizuka, Satoru Yamagami, Kazuno Negishi, Akiharu Kubo, Toshihide Kurihara, 2023.11, 日本網膜硝子体学会, Claudin-1 deficiency in RPE leads to age-related retinal degeneration in mic

  • The Keio Medical Science Rising Star Award

    Toshihide Kurihara, 2023.01, Keio University, Exploring the pathophysiology of the retina and myopia based on photobiology and the clinical adaptation

  • 第72回日本臨床眼科学会学術展示優秀賞

    栗原俊英, 2019.04, 日本眼科学会, 白内障手術患者を対象とした血漿-房水グルコース濃度相関の血糖変動状態による変化

    　View Description

    第123回日本眼科学会総会

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Media Coverage 【 Display / hide 】

  • （扉）遺伝子治療、がんや希少疾患に 患者に合わせ、「土台」応用し費用・期間省く

    朝日新聞社, 朝日新聞 (朝日新聞デジタル) , 2025.10

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    体の細胞の遺伝子操作をする「遺伝子治療」。国内初の実施から３０年たち、多様な治療法が開発され、対象となる病気の種類も増えた。高額な開発費を抑える方法が模索されている。

  • 光遺伝学を活用し、目の難病の視覚再生目指す 慶大など国内初の治験を開始

    サイエンスポータル, 国立研究開発法人 科学技術振興機構, 2025.03

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    神経細胞などの働きを光で制御する「光遺伝学」の手法を活用し、目の難病「網膜色素変性症」で失われた視覚の再生を目指す遺伝子治療薬の臨床試験（治験）を始めた、と慶應義塾大学と名古屋工業大学の共同研究グループが発表した。光遺伝学の臨床応用は国内初という。
    この目の難病は目の内側を覆い、光を受け取って神経の信号に変える働きをする網膜の視細胞が最初に障害を起こし、徐々に機能を失う進行性の失明難病。通常4000人から8000人に1人発症し、根本的な治療法は確立していない。世界の患者は200万人以上とされる。
    慶應大学医学部眼科学教室の栗原俊英准教授らの研究グループは、名古屋工業大学の神取秀樹教授らが開発した「キメラロドプシン」という光に対する感度が高い独自のタンパク質を使い、光遺伝学の手法を応用することで視覚再生効果と視細胞の保護効果があることをマウスで確認し、研究成果を2023年10月に発表していた。
    この成果を生かして慶應大学発のスタートアップ企業「レストアビジョン」（東京都港区）がキメラロドプシンの遺伝子治療薬（視覚再生治療製剤）「RV-001」を開発。栗原准教授らの研究グループは今回、既に視細胞の機能が失われた重症患者1人に対しRV-001を目に注射して1例目の投与を終えた。
    網膜にある双極細胞と呼ばれる神経細胞にキメラロドプシンを作る遺伝子を届け、視細胞の代わりに光の検知を担わせるのが目的。研究グループによると、これまで重い合併症などはないが、今後半年間経過を観察して安全性や有効性を確認する。今後6～15人を対象に治験を続ける予定だ。
    栗原准教授らの研究グループは「（治験を始めたRV-001は）視覚再生治療薬として世界初の実用化を目指す試みで、失明疾患に対する新たな治療法を提供する重要な一歩と位置付けられる」としている。
    光遺伝学は米スタンフォード大学のカール・ダイセロス教授が2005年に技術を確立した。脳研究に大きく貢献し、米国の医学賞であるラスカー賞（基礎分野）の20年授賞者に選ばれ、ノーベル賞の有力候補とされる。
    理化学研究所・脳科学総合研究センターの利根川進センター長（当時）らは2015年に「光遺伝学によってマウスのうつ状態を改善した」と発表した。現在はうつ病や睡眠障害、依存症など精神疾患の仕組みや臓器の働きの制御を研究する分野で活用されている。

  • すんどめ ～網膜色素変性症と生きる〜

    名古屋テレビ放送・テレビ朝日系列全国24社, テレメンタリー2024, 2024.11

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    "すんどめ"の新競技で全国制覇へ！「今を楽しむことが一番」難病がある高校生ボクサーと全盲のシングルマザー 遺伝性のある網膜色素変性症、研究の最前線は

    愛知県岡崎市の石川凌久さんは、“当てないスパーリング”とも呼ばれるマスボクシングに打ち込む高校２年生。母親の智美さんは、２０代で網膜色素変性症という難病で失明した。凌久さんは、高校に入って”殴り合い”がある通常のボクシングをやりたいと思っていたが、受けて失明するのではないかと心配する智美さんの猛反対にあいマスボクシングを選んだ。網膜色素変性症は遺伝する可能性がある。視覚障がい者の選択に光を当てる。
    ナレーター：島貫凌アナウンサー
    名古屋テレビ放送

    https://www.tv-asahi.co.jp/telementary/backnumber/0257/

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Memberships in Academic Societies 【 Display / hide 】

  • The Macular Society, 

    2025.10
    -
    Present

  • Japan Society for Ocular Circulation, 

    2025.04
    -
    Present

  • The Japanese Society for Photomedicine and Photobiology, 

    2023.05
    -
    Present

  • 日本ロービジョン学会, 

    2022.12
    -
    Present

  • 日本人類遺伝学会, 

    2021.07
    -
    Present
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Committee Experiences 【 Display / hide 】

  • 2022.11
    -
    Present

    Associate Editor for Neurodegeneration, Frontiers in Neuroscience

  • 2022.10
    -
    Present

    眼科 外来医長, 慶應義塾大学病院

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