Elucidation of epithelial mesenchymal transition and regeneration of lens in posterior capsule opacity after cataract surgery.

• Project/Area Number: 26462672
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kanazawa Medical University
• Principal Investigator: KUBO Eri 金沢医科大学, 医学部, 教授 (10262619)
• Research Collaborator: YOSHINO Ayaka ; OCHIAI Kana
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 後発白内障 / トロポミオシン / 上皮間葉系移行 / 創傷治癒 / 水晶体上皮細胞 / 後嚢混濁 / FGF

Outline of Final Research Achievements

In this study, we revealed that Tpm1/2 was related to progression of rat PCO after cataract surgery and other processes of EMT such as wound healing. We showed that stress fiber formation in MLEC induced by EMT could be reversed by FGF2 and Tpm1/2 siRNA transfection. Our results revealed involvement of FGF2-MAPK pathway in FGF2-mediated inhibition of Tpm expression. Furthermore, we investigated the role of Tpm2 in PCO, EMT and lens opacity by generating Tpm2 hetero-knock-out mice. Since Tpm2 is involved in the progression of EMT in LEC wound healing its inhibition may suppress PCO.

Research Products

• [Journal Article] FGF2 antagonizes aberrant TGFβ regulation of Tropomyosin: Role for posterior capsule opacity. (2017)
  • Author(s): Kubo E, Shibata S, Shibata T, Kiyokawa E, Sasaki H, Singh DP.
  • Journal Title: J Cell Mol Med Volume: 21(5) Issue: 5 Pages: 916-928
  • DOI: 10.1111/jcmm.13030
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Tropomyosin 2: Its relationship with age-related-cataract and posterior capsular opacification. (2016)
  • Author(s): Eri Kubo
  • Organizer: XXII Biennial Meeting of the International Society of Eye Research
  • Place of Presentation: 京王プラザホテル(東京都新宿区)
  • Year and Date: 2016-09-25
  • Int'l Joint Research / Invited
• [Presentation] Tpm2KOマウスによる水晶体の蛋白発現と組織変化 (2016)
  • Author(s): 柴田哲平、柴田伸亮、柴田奈央子、石垣 靖人、清川悦子、伊川正人、佐々木洋、久保江理
  • Organizer: 第55回日本白内障学会総会
  • Place of Presentation: いわて県民情報交流センター アイーナ(岩手県盛岡市)
  • Year and Date: 2016-07-29
• [Presentation] Knock-Down of Tropomyosin 2 Created By CRISPR-CAS9 in Mouse Induces Age-Related-Cataract (2016)
  • Author(s): Eri Kubo, Teppei Shibata, Shinsuke Shibata, Hiroshi Sasaki, Etsuko Kiyokawa, Masahito Ikawa, Dhirendra P Singh
  • Organizer: The Association for Research in Vision and Ophthalmology (ARVO) 2016
  • Place of Presentation: Washington State Convention Center, Seattle,USA
  • Year and Date: 2016-05-01
  • Int'l Joint Research
• [Presentation] Knock-down of tropomyosin 2 created by CRISPR-CAS9 in mouse induced age-related cataract (2016)
  • Author(s): Eri Kubo, Teppei Shibata, Shinsuke Shibata, Hiroshi Sasaki, Etsuko Kiyokawa, Masahito Ikawa, Dhirendra P Singh
  • Organizer: The Association for Research in Vision and Ophthalmology (ARVO) 2016
  • Place of Presentation: Washington State Convention Center, Seattle, USA
  • Year and Date: 2016-05-01
  • Int'l Joint Research
• [Presentation] Tropomyosin and its relationship with posterior capsular opacity (2016)
  • Author(s): Eri Kubo
  • Organizer: 日本眼科学会総会
  • Place of Presentation: 仙台国際センター・東北大学百周年記念会館 (宮城県仙台市)
  • Year and Date: 2016-04-07
• [Presentation] CRISPR-Cas9システムを用いたTpm2ノックアウトマウスの白内障 (2016)
  • Author(s): 柴田哲平、柴田伸亮、柴田奈央子、石垣 靖人、清川悦子、伊川正人、佐々木洋、久保江理
  • Organizer: 日本眼科学会総会
  • Place of Presentation: 仙台国際センター・東北大学百周年記念会館 (宮城県仙台市)
  • Year and Date: 2016-04-07
• [Presentation] Tropomyosin and its relationship with posterior capsular opacity (2016)
  • Author(s): Eri Kubo
  • Organizer: 第120回日本眼科学会総会
  • Place of Presentation: 仙台国際センター（宮城県、仙台市）
  • Year and Date: 2016-04-07
  • Invited
• [Presentation] Gene expression profiling of lens epithelial cells in posterior capsule opacity and the role of decorin (2015)
  • Author(s): Eri Kubo
  • Organizer: The3rd International Conference of the Lens
  • Place of Presentation: Sheraton Kona Resort & Spa At Keauhou Bay, Kona, USA
  • Year and Date: 2015-12-06
  • Int'l Joint Research / Invited
• [Presentation] Suppression of injury-induced epithelial-mesenchymal transition in tropomyosin 2 mutant mouse lens created by CRISPR-CAS9 (2015)
  • Author(s): Teppei Shibata, Shinsuke Shibata, Hiroshi Sasaki, Dhirendra P Singh, Etsuko Kiyokawa, Masahito Ikawa, Eri Kubo
  • Organizer: The3rd International Conference of the Lens
  • Place of Presentation: Sheraton Kona Resort & Spa At Keauhou Bay, Kona, USA
  • Year and Date: 2015-12-06
  • Int'l Joint Research
• [Presentation] CRISPR-Cas9システムを用いたTpm2ノックアウトマウスによる後発白内障研究 (2015)
  • Author(s): 柴田哲平、柴田伸亮、柴田奈央子、清川悦子、伊川正人、佐々木洋、久保江理
  • Organizer: 第54回白内障学会
  • Place of Presentation: ミッドランドホール（愛知県、名古屋市）
  • Year and Date: 2015-09-18
• [Presentation] FGF-2 regression of the tropomyosin expression through MAPK/ERK kinase pathway in lens epithelial cells (2015)
  • Author(s): Teppei Shibata, Shinsuke Shibata, Naoko Shibata, Etsuko Kiyokawa, Hiroshi Sasaki, Dhirendra P Singh, Eri Kubo
  • Organizer: ARVO (The association for research in vision and ophthalmology)2015
  • Place of Presentation: Corolado convention center, Denver, Colorado, USA
  • Year and Date: 2015-05-03 – 2015-05-07
• [Presentation] Gene expression profiling of lens epithelial cells in a rat posterior capsular opacity model in vivo (2015)
  • Author(s): Eri Kubo, Shinsuke Shibata, Naoko Shibata, Teppei Shibata, Etsuko Kiyokawa, Hiroshi Sasaki, Dhirendra P Singh
  • Organizer: The Association for Research in Vision and Ophthalmology (ARVO) 2015
  • Place of Presentation: Colorado Convention Center, Denver, USA
  • Year and Date: 2015-05-03
  • Int'l Joint Research
• [Presentation] Regulation of Epithelial Mesenchymal Transition (EMT): Suppression of Posterior Capsular Opacification (PCO) (2015)
  • Author(s): Eri Kubo
  • Organizer: Asia-ARVO(The association for research in vision and ophthalmology)2015
  • Place of Presentation: Pacifico Yokohama, Yokohama, Japan
  • Year and Date: 2015-02-16 – 2015-02-19
  • Invited
• [Presentation] FGF2によるトロポミオシン発現抑制のメカニズム (2014)
  • Author(s): 柴田哲平、長田ひろみ、柴田伸亮、清川悦子、佐々木洋、久保江理
  • Organizer: 第53回日本白内障学会総会
  • Place of Presentation: TKPガーデンシティ品川、東京
  • Year and Date: 2014-09-27 – 2014-09-28