Relationship and functional analysis of proteoglycan decorin in posterior capsule opacification

• Project/Area Number: 16K20336
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Kanazawa Medical University
• Principal Investigator: SHIBATA Shinsuke 金沢医科大学, 医学部, 助教 (30440514)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 眼生化学・分子生物 / 眼生化学・分子生物学

Outline of Final Research Achievements

We demonstrated that the expression of proteoglycan decorin (DCN) was highly upregulated by analyzing gene expression using DNA microarray in lens epithelial cells (LEC) from a rat postoperative posterior capsule opacification (PCO) model. Further, genes related with epithelial-mesenchymal transition (EMT) and those related with the differentiation of lens fiber were upregulated. DCN was also detected in human anterior aqueous. DCN gene expression level in human LEC and DCN concentration in human anterior aqueous did not correlate with age, opacity type or grade. In cultured mouse and human LECs, DCN mRNA was upregulated concentration-dependently after treatment fibroblast growth factor 2 (FGF2) and decreased with treatment of transforming growth factor β2 (TGFβ2).
In conclusion, DCN may be related with EMT and lens fiber differentiation in PCO development.

Academic Significance and Societal Importance of the Research Achievements

白内障術後の後嚢混濁（PCO）の治療にはYAGレーザーによる後嚢切開術があるが、術後の網膜裂孔形成やぶどう膜炎、眼圧上昇といった合併症が問題となる。我々は、ラット水晶体摘出術後のPCO組織で、プロテオグリカンの１つであるデコリン(DCN)が高発現であることを見出した。本研究では、このDCNの分子機構を解明し、PCOとの関わりを明らかにすることを目的とする。

Research Products

• [Journal Article] The role of Prdx6 in the protection of cells of the crystalline lens from oxidative stress induced by UV exposure (2016)
  • Author(s): S.Shibata,N,Shibata,T.Shibata,H.Sasaki,DS.Singh,E,Kubo
  • Journal Title: Japanese Journal of Ophthalmology Volume: 60 Issue: 5 Pages: 408-418
  • DOI: 10.1007/s10384-016-0461-1
  • Peer Reviewed
• [Presentation] Expression of proteoglycan decorin in opacified posterior capsule and its suppression by TGF βin mouse lens epithelial cells (2018)
  • Author(s): S.Shibata, N.Shibata, T.Shibata, H.Ishida, E.Kiyokawa, H.Sasaki, E.Kubo
  • Organizer: The Association for Research in Vision and Ophthalmology
• [Presentation] マウス後嚢混濁モデルの作成とプロテオグリカンdecoeinの発現変化 (2018)
  • Author(s): 柴田伸亮、柴田奈央子、柴田哲平、石田秀俊、清川悦子、佐々木洋、久保江理
  • Organizer: 第1２２回日本眼科学会総会
• [Presentation] 水晶体特異的トロポミオシン１ノックアウトによる水晶体混濁 (2018)
  • 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1２２回日本眼科学会総会
• [Presentation] Effects of proteoglycan decorin on lens epithelial cells (2017)
  • Author(s): S.Shibata,N.Shiata,T.Shibata,N.Tanimura,H.Sasaki,E.Kubo
  • Organizer: The Association for Research in Vision and Ophthalmology
  • Place of Presentation: Baltimore Convention Center (ボルチモア・米国）
  • Year and Date: 2017-05-07
• [Presentation] プロテオグリカンDecorinの水晶体上皮細胞への影響 (2017)
  • Author(s): 柴田伸亮、柴田奈央子、柴田哲平、谷村直紀、佐々木洋、久保江理
  • Organizer: 第121回日本眼科学会
  • Place of Presentation: 東京国際フォーラム （東京都千代田区）
  • Year and Date: 2017-04-06
• [Presentation] Age-related cataract and expression level of decorin in human eye:association with opacity severity (2016)
  • Author(s): S.Shibata,N.Shibata,T.Shibata,N.Tanimura,H.Sasaki,E.Kubo
  • Organizer: The Association for Research in Vision and Ophthalmology
  • Place of Presentation: Washington Sate Convention (シアトル ・米国)
  • Year and Date: 2016-05-01
• [Presentation] プロテオグリカン decorinのヒト房水と水晶体上皮細胞における発現と白内障との関係 (2016)
  • Author(s): 柴田伸亮、柴田奈央子、柴田哲平、谷村直紀、佐々木洋、久保江理
  • Organizer: 第120回日本眼科学会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2016-04-07