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Transplantation of retinal ganglion cells generated from iPS and ES cells

Research Project

Project/Area Number 15K15640
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Ophthalmology
Research InstitutionNational Center for Child Health and Development

Principal Investigator

Azuma Noriyuki  国立研究開発法人国立成育医療研究センター, 感覚器・形態外科部, 医長 (10159395)

Co-Investigator(Kenkyū-buntansha) 横井 匡  国立研究開発法人国立成育医療研究センター, 感覚器・形態外科部, 医師 (80514025)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords視神経 / 網膜神経節細胞 / iPS細胞 / ES細胞 / 再生医学 / 軸索 / 細胞移植
Outline of Final Research Achievements

We generated self-induced retinal ganglion cells (RGCs) with functional axons from human and murine iPS and ES cells. Axons extended radially from the margin of the clump. Induced RGCs expressed specific markers by quantitative PCR and immunohistochemistry. The long, prominent axons contained neurofilaments and tau, and manifested anterograde axonal transport and sodium-dependent action potentials. The ability to generate RGCs with functional axons uniformly and at a high rate may contribute to treatment of various optic nerve diseases that threaten vision. We transplanted the RGCs into the murine retina after damaging the optic nerve. The RGCs were successfully engrafted and radiated their axons into the damaged optic nerve. Pathfinding of axons were in vitro evaluated by slow release of Sem3A and Slit1 from beads inserted in the colony of RGCs. Axons were bended in accordance with guidance of chemical agents.
These finding suggests a possibility of transplantation of RGCs.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (52 results)

All 2017 2016 2015

All Journal Article (21 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 21 results,  Open Access: 15 results) Presentation (29 results) (of which Int'l Joint Research: 1 results,  Invited: 8 results) Book (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] A. Anteroposterior Patterning of Gene Expression in the Human Infant Sclera: Chondrogenic Potential and Wnt Signaling.2017

    • Author(s)
      Seko Y, Azuma N, Yokoi T, Kami D, Ishii R, Nishina S, Toyoda M, Shimokawa H, Umezawa
    • Journal Title

      Curr Eye Res

      Volume: 42(1) Issue: 1 Pages: 145-154

    • DOI

      10.3109/02713683.2016.1143015

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Different foveal schisis patterns in each retinal layer in eyes with hereditary juvenile retinoschisis evaluated by en-face optical coherence tomography.2017

    • Author(s)
      Yoshida-Uemura T, Katagiri S, Yokoi T, Nishina S, Azuma N.
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol.

      Volume: 255(4) Issue: 4 Pages: 719-723

    • DOI

      10.1007/s00417-016-3552-2

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical features of a toddler with bilateral bullous retinoschisis with a novel RS1 mutation.2017

    • Author(s)
      Katagiri S, Tanaka S, Yokoi T, Hayashi T, Matsuzaka E, Ueda K, Yoshida-Uemura T, Arakawa A, Nishina S, Kadonosono K, Azuma N.
    • Journal Title

      American Journal of Ophthalmology Case Reports

      Volume: 5 Pages: 76-80

    • DOI

      10.1016/j.ajoc.2016.12.009

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genotype-phenotype correlation of the PAX6 gene mutations in aniridia2016

    • Author(s)
      Yokoi T, Nishina S, Fukami M, Ogata T, Hosono K, Hotta Y, Azuma N.
    • Journal Title

      Human Genome Variation

      Volume: 3 Issue: 1 Pages: 15052-15052

    • DOI

      10.1038/hgv.2015.52

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] he role of vitreoretinal traction in the pathogenesis of maculopathy associated with optic disc pits.2016

    • Author(s)
      Yokoi T, Nakayama Y, Nishina S, Azuma N.
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol.

      Volume: 254 Issue: 9 Pages: 1859-1860

    • DOI

      10.1007/s00417-016-3380-4

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of retinal ganglion cells with functional axons from mouse embryonic stem cells and induced pluripotent stem cells.2016

    • Author(s)
      Tanaka T, Yokoi T, Tamalu F, Watanabe S, Nishina S, Azuma N.
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 57 Issue: 7 Pages: 3348-3359

    • DOI

      10.1167/iovs.16-19166

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful scleral buckling of late-onset visual decrease in eye with retinal folds.2016

    • Author(s)
      Nakayama Y, Katagiri S, Yokoi T, Ui M, Nishina S, Azuma N
    • Journal Title

      Doc Ophthalmol.

      Volume: 133 Issue: 2 Pages: 145-149

    • DOI

      10.1007/s10633-016-9559-5

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Outer retinal deformity detected by optical coherence tomography in eyes with foveal hypoplasia.2016

    • Author(s)
      Katagiri S, Yokoi T, Mikami M, Nishina S, Azuma N.
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol.

      Volume: 254 Issue: 11 Pages: 2197-2201

    • DOI

      10.1007/s00417-016-3385-z

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Electroretinographic effects of retinal dragging and retinal folds in eyes with familial exudative vitreoretinopathy.2016

    • Author(s)
      Yaguchi Y, Katagiri S, Fukushima Y, Yokoi T, Nishina S, Kondo M, Azuma N.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 30523-30523

    • DOI

      10.1038/srep30523

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The mevalonate pathway regulates primitive streak formation via protein farnesylation2016

    • Author(s)
      Okamoto-Uchida Y, Yu R, Miyamura N, Arima N, Ishigami-Yuasa M, Kagechika H, Yoshida S, Hosoya T, Nawa M, Kasama T, Asaoka Y, Alois RW, Elling U, Penninger JM, Nishina S, Azuma N, Nishina H
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 37697-37697

    • DOI

      10.1038/srep37697

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structure and morphology of radial retinal folds with familial exudative vitreoretinopathy.2016

    • Author(s)
      Katagiri S, Yokoi T, Nishina S, Azuma N.
    • Journal Title

      Ophthalmology

      Volume: 123(3) Issue: 3 Pages: 666-8

    • DOI

      10.1016/j.ophtha.2015.09.010

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Abnormal traction of the vitreous detected by swept-source optical coherence tomography is related to the maculopathy associated with optic disc pits.2016

    • Author(s)
      Yokoi T, Nakayama Y, Nishina S, Azuma N.
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol.

      Volume: in press Issue: 4 Pages: 675-682

    • DOI

      10.1007/s00417-015-3114-z

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of retinal ganglion cells with functional axons from human induced pluripotent stem cells2015

    • Author(s)
      Taku Tanaka, Tadashi Yokoi, Fuminobu Tamalu, Shu-Ichi Watanabe, Sachiko Nishina and Noriyuki Azuma
    • Journal Title

      Scientific Reports

      Volume: 10(5) Issue: 1 Pages: 8344-8344

    • DOI

      10.1038/srep08344

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical characteristics of congenital and developmental cataract undergoing surgical treatment2015

    • Author(s)
      Nagamoto T, Oshika T, Fujikado T, Ishibashi T, Sato M, Kondo M, Kurosaka D, Azuma N.
    • Journal Title

      Jpn J Ophthalmol

      Volume: 59 Issue: 3 Pages: 148-56

    • DOI

      10.1007/s10384-015-0370-8

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A survey of the surgical treatment of congenital and developmental cataracts in Japan2015

    • Author(s)
      Nagamoto T, Oshika T, Fujikado T, Ishibashi T, Sato M, Kondo M, Kurosaka D, Azuma N
    • Journal Title

      Jpn J Ophthalmol

      Volume: 59 Issue: 4 Pages: 203-8

    • DOI

      10.1007/s10384-015-0385-1

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 先天眼疾患における両眼視機能.2015

    • Author(s)
      八木橋めぐみ, 仁科幸子, 萬束恭子, 鹿田千尋, 新保由紀子, 赤池祥子, 越後貫滋子, 上村朋世, 横井 匡, 東 範行
    • Journal Title

      眼臨紀

      Volume: 8(8) Pages: 564-570

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 特集 小児眼科診療のコツと注意点.2015

    • Author(s)
      東 範行
    • Journal Title

      OCULISTA

      Volume: 7 Pages: 1-77

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 特集 視覚障害の早期発見と治療.2015

    • Author(s)
      東 範行・寺崎浩子
    • Journal Title

      日本医師会雑誌

      Volume: 14 Pages: 1765-1835

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 小児と成人の視力を脅かす疾患と治療の展望.2015

    • Author(s)
      寺崎浩子・川崎 良・石橋達朗・東 範行
    • Journal Title

      日本医師会雑誌

      Volume: 14 Pages: 1765-1765

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 視力の確保は早期発見と的確な治療から.2015

    • Author(s)
      東 範行
    • Journal Title

      日本医師会雑誌

      Volume: 14 Pages: 1765-1765

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 単細胞生物の眼の構造は別々に起こった細胞内共生によって獲得された.2015

    • Author(s)
      東 範行
    • Journal Title

      日本の眼科

      Volume: 86 Pages: 1578-1579

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Swept-Source OCT Images of Morning Glory Disc Anomaly and Allied Diseases. Distinguished Papers Symposium2016

    • Author(s)
      Yoshida T, Katagiri S, Yokoi T, Nishina S, Azuma N.
    • Organizer
      第55回日本網膜硝子体学会
    • Place of Presentation
      ベルサール渋谷ガーデン(東京)
    • Year and Date
      2016-12-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] RPGRIP1遺伝子異常によるLeber先天盲の1家系3症例の臨床像2016

    • Author(s)
      宮道大督、仁科幸子、細野克博、横井匡、倉田健太郎、彦谷明子、簑島伸生、佐藤美保、深見真紀、堀田喜裕、東範行
    • Organizer
      第55回日本網膜硝子体学会
    • Place of Presentation
      ベルサール渋谷ガーデン(東京)
    • Year and Date
      2016-12-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] 網脈絡膜コロボーマのSwept-Source光干渉断層計像.2016

    • Author(s)
      富田匡彦、横井匡、吉田朋世、高橋真理、片桐聡、仁科幸子、東範行
    • Organizer
      第70回日本臨床眼科学会
    • Place of Presentation
      京都国際会議場(京都)
    • Year and Date
      2016-11-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] 家族性滲出性硝子体網膜症の黄斑上膜に硝子体手術を行った4例2016

    • Author(s)
      高橋真理、富田匡彦、吉田朋世、片桐聡、横井匡、仁科幸子、東範行
    • Organizer
      第70回日本臨床眼科学会
    • Place of Presentation
      京都国際会議場(京都)
    • Year and Date
      2016-11-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] 斜視を伴う小児に対するSpot Vision Screenerの使用経験.2016

    • Author(s)
      萬束恭子、松岡真未、新保由紀子、赤池祥子、越後貫滋子、片桐聡、吉田朋世、横井匡、仁科幸子、東範行
    • Organizer
      第57回日本視能矯正学会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Year and Date
      2016-10-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] iPS細胞・ES細胞からの視神経細胞の誕生と臨床応用2016

    • Author(s)
      東範行
    • Organizer
      第57回日本視能矯正学会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Year and Date
      2016-10-15
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 乳児内斜視早期手術後の両眼視機能2016

    • Author(s)
      吉田朋世、仁科幸子、横井匡、鹿田千尋、萬束恭子、赤池祥子、越後貫滋子、東範行
    • Organizer
      第72回日本弱視斜視学会総会・第41回日本小児眼科学会総会合同学会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2016-06-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] 次世代シークエンサーを用いたレーバー先天盲の1家系3症例の遺伝子変異解析2016

    • Author(s)
      細野克博、仁科幸子、宮道大督、横井匡、彦谷明子、佐藤美保、簑島伸生、深見真紀、東範行、堀田喜裕
    • Organizer
      第72回日本弱視斜視学会総会・第41回日本小児眼科学会総会合同学会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2016-06-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] Roles of Genes in Phenotypic Diversity and Interocular Asymmetry in Patients with Familial Exudative Vitreoretinopathy.2016

    • Author(s)
      Kondo H, Uchio E, Hayashi T, Nishina S, Azuma N, Kusaka S.
    • Organizer
      2016 Annual Meeting, Association for Research in Vision and Ophthalmology
    • Place of Presentation
      Seattle, U.S.A
    • Year and Date
      2016-05-01
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 小児眼底疾患の構造と機能の検査による病態の理解2016

    • Author(s)
      東範行
    • Organizer
      第120回日本眼科学会総会
    • Place of Presentation
      仙台国際センター(宮城)
    • Year and Date
      2016-04-07
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Distinguished papaers symposium 1.:Detailed structure and morphology from retinal dragging to radial retinal folds associated with familial exudative vitreoretinopathy.2015

    • Author(s)
      Katagiri S, Yokoi T, Nishina S, Azuma N.
    • Organizer
      第54回日本網膜硝子体学会
    • Place of Presentation
      東京国際フォーラム(東京・千代田区)
    • Year and Date
      2015-12-04
    • Related Report
      2015 Research-status Report
  • [Presentation] iPS細胞による視神経の研究2015

    • Author(s)
      東 範行
    • Organizer
      第36回西中国眼疾患フォーラム.
    • Place of Presentation
      ANAクラウンプラザホテル宇部( 山口・宇部市)
    • Year and Date
      2015-11-26
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 小児眼疾患の診かた・考え方2015

    • Author(s)
      東 範行
    • Organizer
      東京都眼科医会卒後研修会
    • Place of Presentation
      東京都眼科医会(東京・新宿区)
    • Year and Date
      2015-11-07
    • Related Report
      2015 Research-status Report
  • [Presentation] 小児眼科の最近の進歩2015

    • Author(s)
      東 範行
    • Organizer
      第9回Midland Seninar of Ophthalmology.
    • Place of Presentation
      名古屋マリオットアソシアホテル(愛知・名古屋市)
    • Year and Date
      2015-11-07
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] iPS細胞とES細胞からの網膜神経節細胞の作製2015

    • Author(s)
      東 範行
    • Organizer
      第8回Retina Research Meeting.
    • Place of Presentation
      JRタワーホール&カンファレンス(東京・千代田区)
    • Year and Date
      2015-10-31
    • Related Report
      2015 Research-status Report
  • [Presentation] シンポジウム 眼科臨床の最先端-失明者ゼロを目指して. 未熟児網膜症.2015

    • Author(s)
      東 範行
    • Organizer
      第69回日本臨床眼科学会
    • Place of Presentation
      名古屋国際会議場(愛知・名古屋市)
    • Year and Date
      2015-10-22
    • Related Report
      2015 Research-status Report
  • [Presentation] 両眼の収縮性乳頭周囲ぶどう腫の1例2015

    • Author(s)
      上村朋世、横井匡、仁科幸子、東 範行
    • Organizer
      第69回日本臨床眼科学会
    • Place of Presentation
      名古屋国際会議場(愛知・名古屋市)
    • Year and Date
      2015-10-22
    • Related Report
      2015 Research-status Report
  • [Presentation] 小児の発達緑内障の治療成績に関する検討2015

    • Author(s)
      小澤紘子、山根みお、上村朋世、八木橋めぐみ、片桐聡、横井匡、中山百合、仁科幸子、東 範行
    • Organizer
      第69回日本臨床眼科学会
    • Place of Presentation
      名古屋国際会議場(愛知・名古屋市)
    • Year and Date
      2015-10-22
    • Related Report
      2015 Research-status Report
  • [Presentation] 新しい視神経疾患の治療の展望―iPS細胞を用いた再生医療と創薬―2015

    • Author(s)
      東 範行
    • Organizer
      第16回神奈川県眼科学術講演会
    • Place of Presentation
      ホテルキャメロットジャパン(神奈川・横浜市)
    • Year and Date
      2015-09-26
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] セミナー 創薬を目指した眼科研究. ヒトiPS細胞を用いた視神経疾患に対する創薬の研究.2015

    • Author(s)
      東 範行
    • Organizer
      第35回日本眼薬理学会モーニングセミナー
    • Place of Presentation
      ソラシティホール(東京・千代田区)
    • Year and Date
      2015-09-06
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] iPS細胞を用いた視神経の研究2015

    • Author(s)
      東 範行
    • Organizer
      愛知県眼科医会第3回学術研修会
    • Place of Presentation
      愛知県医師会館(愛知・名古屋市)
    • Year and Date
      2015-08-29
    • Related Report
      2015 Research-status Report
  • [Presentation] iPS細胞とES細胞からの網膜神経節細胞の作製.2015

    • Author(s)
      東 範行
    • Organizer
      第17回 Japan Macula Club.
    • Place of Presentation
      蒲郡クラシックホテル(愛知・蒲郡市)
    • Year and Date
      2015-08-22
    • Related Report
      2015 Research-status Report
  • [Presentation] 眼の発生と遺伝.2015

    • Author(s)
      東 範行
    • Organizer
      平成27年夏 合同症例検討会
    • Place of Presentation
      順天堂大学(東京・文京区)
    • Year and Date
      2015-08-01
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 先天眼疾患における黄斑異常と両眼視機能2015

    • Author(s)
      仁科幸子、八木橋めぐみ、萬束恭子、鹿田千尋、赤池祥子、越後貫滋子、上村朋世、横井匡、東 範行.
    • Organizer
      第71回日本弱視斜視学会総会・第40回日本小児眼科学会総会合同学会
    • Place of Presentation
      ポートピアホテル(兵庫・神戸市)
    • Year and Date
      2015-07-03
    • Related Report
      2015 Research-status Report
  • [Presentation] 急性網膜壊死が疑われた眼サルコイドーシスの一例.2015

    • Author(s)
      上村朋世、八木橋めぐみ、横井匡、仁科幸子、東 範行
    • Organizer
      第71回日本弱視斜視学会総会・第40回日本小児眼科学会総会合同学会
    • Place of Presentation
      ポートピアホテル(兵庫・神戸市)
    • Year and Date
      2015-07-03
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒトiPS細胞から網膜神経節細胞の作製.2015

    • Author(s)
      東 範行
    • Organizer
      第71回日本弱視斜視学会総会・第40回日本小児眼科学会総会合同学会 千寿製薬研究所セミナー
    • Place of Presentation
      ポートピアホテル(兵庫・神戸市)
    • Year and Date
      2015-07-03
    • Related Report
      2015 Research-status Report
  • [Presentation] 小児眼科分野の最近の話題.2015

    • Author(s)
      東 範行
    • Organizer
      第8回Tokyo West Ophthalmic Conference
    • Place of Presentation
      渋谷エクセルホテル東急(東京・渋谷区)
    • Year and Date
      2015-05-13
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] サブスペシャリティーサンデー 「視機能・小児眼科・眼腫瘍」2015

    • Author(s)
      東 範行
    • Organizer
      第119回日本眼科学会総会
    • Place of Presentation
      ロイトン札幌(北海道・札幌市)
    • Year and Date
      2015-04-16
    • Related Report
      2015 Research-status Report
  • [Presentation] Best of AAO 弱視斜視・小児・神経眼科2015

    • Author(s)
      仁科幸子
    • Organizer
      第119回日本眼科学会総会
    • Place of Presentation
      ロイトン札幌(北海道・札幌市)
    • Year and Date
      2015-04-16
    • Related Report
      2015 Research-status Report
  • [Book] 小児眼科学2015

    • Author(s)
      東 範行
    • Total Pages
      570
    • Publisher
      三輪書店(東京)
    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] 視神経細胞の作製方法2015

    • Inventor(s)
      東 範行・横井 匡・田中 卓
    • Industrial Property Rights Holder
      国立成育医療研究センター・千寿製薬
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-08-07
    • Related Report
      2015 Research-status Report
    • Overseas

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Published: 2015-04-16   Modified: 2018-03-22  

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