Development of molecular targeting therapy for diabetic retionopathy based on gene expression profiling of fibrovascular membranes

• Project/Area Number: 23592574
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kyushu University
• Principal Investigator: YOSHIDA Shigeo 九州大学, 医学(系)研究科(研究院), 講師 (50363370)
• Co-Investigator(Kenkyū-buntansha): ISHIBASHI Tatsuro 九州大学, 医学研究院, 教授 (30150428) ; KONO Toshihiro 福岡大学, 医学部, 講師 (80580315)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ゲノムワイド遺伝子発現解析 / ペリオスチン / 増殖糖尿病網膜症 / 増殖硝子体網膜症 / 核酸医薬 / 糖尿病網膜症

Research Abstract

We found increased periostin expression in the vitreous of patients with proliferative diabetic retinopathy (PDR). Immunohistochemical analysis showed colocalization of periostin and a-SMA in PDR-ERMs. In vitro, periostin increased proliferation, adhesion, migration, and collagen production in RPE cells. Periostin blockade suppressed migration and adhesion induced by TGFb2. In vivo, periostin inhibition had the inhibitory effect on experimental retinal fibrovascular formartion without affecting the viability of retinal cells. These results identified periostin as a pivotal molecule for ERM formation as well as a promising therapeutic target for PDR.

Research Products

• [Journal Article] Periostin promotes the generation of fibrous membranes in proliferative vitreoretinopathy (2014)
  • Author(s): Ishikawa K, Yoshida S, Nakao S, Nakama T, Kita T, Asato R, Sassa Y, Arita R, Miyazaki M, Enaida H, Oshima Y, Murakami N, Niiro H, Ono J, Matsuda A, Goto Y, Akashi K, Izuhara K, Kudo A, Kono T, Hafezi-Moghadam A, and Ishibashi T
  • Journal Title: FASEB J Volume: 28 Pages: 131-142
• [Journal Article] Periostin promotes the generation of fibrous membranes in proliferative vitreoretinopathy (2014)
  • Author(s): Ishikawa K, Yoshida S, Nakao S, Nakama T, Kita T, Asato R, Sassa Y, Arita R, Miyazaki M, Enaida H, Oshima Y, Murakami N, Niiro H, Ono J, Matsuda A, Goto Y, Akashi K, Izuhara K, Kudo A, Kono T, Hafezi-Moghadam A, Ishibashi T.
  • Journal Title: FASEB J Volume: 28 Issue: 1 Pages: 131-142
  • DOI: 10.1096/fj.13-229740
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of gene expression profile of epiretinal membranes obtained from eyes with proliferative vitreoretinopathy to that of secondary epiretinal membranes (2013)
  • Author(s): Asato R, Yoshida S, Ogura A, Nakama T, Ishikawa K, Nakao S, Sassa Y, Enaida H, Oshima Y, Ikeo K, Gojobori T, Kono T, and Ishibashi T
  • Journal Title: PLoS One Volume: 8
  • NAID: 120005227330
• [Journal Article] Comparison of gene expression profile of epiretinal membranes obtained from eyes with proliferative vitreoretinopathy to that of secondary epiretinal membranes (2013)
  • Author(s): Asato R, et. al.
  • Journal Title: PLoS One. Volume: 8 Issue: 1 Pages: e54191-e54191
  • DOI: 10.1371/journal.pone.0054191
  • Peer Reviewed
• [Journal Article] Antiangiogenic shift in vitreous after vitrectomy in patients with proliferative diabetic retinopathy (2012)
  • Author(s): Yoshida S, Nakama T, Ishikawa K, Arima M, Tachibana T, Nakao S, Sassa Y, Yasuda M, Enaida H, Oshima Y, Kono T, and Ishibashi T
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 53 Pages: 6997-7003
• [Journal Article] Bone marrow-derived monocyte lineage cells recruited by MIP-1beta promote physiological revascularization in mouse model of oxygen-induced retinopathy (2012)
  • Author(s): Ishikawa K, Yoshida S, Nakao S, Sassa Y, Asato R, Kohno R, Arima M, Kita T, Yoshida A, Ohuchida K, and Ishibashi T
  • Journal Title: Lab Invest Volume: 92 Pages: 91-101
• [Journal Article] Involvement of periostin in regression of hyaloidvascular system during ocular development (2012)
  • Author(s): Arima M, Yoshida S, Nakama T, Ishikawa K, Nakao S, Yoshimura T, Asato R, Sassa Y, Kita T, Enaida H, Oshima Y, Matsuda A, Kudo A, and Ishibashi T
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 53 Pages: 6495-6503
• [Journal Article] Involvement of periostin in regression of hyaloidvascular system during ocular development (2012)
  • Author(s): Arima M, et al.
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: 53 Issue: 10 Pages: 6495-6503
  • DOI: 10.1167/iovs.12-9684
  • Peer Reviewed
• [Journal Article] Increased expression of periostin in vitreous and fibrovascular membranes obtained from patients with proliferative diabetic retinopathy (2011)
  • Author(s): Yoshida S, Ishikawa K, Asato R, Arima M, Sassa Y, Yoshida A, Yoshikawa H, Narukawa K, Obika S, Ono J, Ohta S, Izuhara K, Kono T, and Ishibashi T
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 52 Pages: 5670-5678
• [Journal Article] Increased expression of periostin in vitreous and fibrovascular membranes obtained from patients with proliferative diabetic retinopathy (2011)
  • Author(s): Yoshida, S. Ishikawa, K. Asato, R. Arima, M. Sassa, Y. Yoshida, A. Yoshikawa, H. Narukawa, K. Obika, S. Ono, J. Ohta, S. Izuhara, K. Kono, T. Ishibashi, T.
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 52 Pages: 5670-8
  • Peer Reviewed
• [Presentation] 糖尿病網膜症に対する分子標的治療 (2014)
  • Author(s): 吉田茂生
  • Organizer: 第24回やまがたDM meeting
  • Place of Presentation: 山形市
  • Year and Date: 2014-03-01
• [Presentation] 糖尿病網膜症の薬物治療 (2014)
  • Author(s): 吉田茂生
  • Organizer: 第11回福島糖尿病眼研究会
  • Place of Presentation: 郡山市
  • Year and Date: 2014-02-08
• [Presentation] ゲノム医科学的アプローチによる増殖性網膜硝子体疾患の責任遺伝子同定と治療への展開 (2013)
  • Author(s): 吉田茂生
  • Organizer: 第117回日本眼科学会総会
  • Place of Presentation: 東京都
  • Year and Date: 2013-04-06
• [Presentation] 網膜硝子体サンプルが教えてくれる次世代医療へのヒント (2012)
  • Author(s): 吉田茂生
  • Organizer: 第93回秋田県眼科集談会
  • Place of Presentation: 秋田市
  • Year and Date: 2012-12-09
• [Presentation] The role of M2 macrophages in the development of fibrovascular membranes in diabetic retinopathy (2012)
  • Author(s): Yoshida S
  • Organizer: The Fifth Joint Meeting of Korea-China-Japan Ophthalmologists
  • Place of Presentation: Fukuoka
  • Year and Date: 2012-11-17
• [Presentation] Fibrovascular membranes associated with PDR : Identification of molecular targets by global gene expression profiling (2012)
  • Author(s): Yoshida Shigeo
  • Organizer: The Third Kyushu-Youngnam Retina Meeting
  • Place of Presentation: Busan
  • Year and Date: 2012-08-18
• [Presentation] 遺伝性眼疾患の基本知識 (2011)
  • Author(s): 吉田茂生
  • Organizer: 第4回愛知県眼科医会学術講演会
  • Place of Presentation: 名古屋市
  • Year and Date: 2011-11-12
• [Presentation] 糖尿病合併症の克服を目指して-基礎から臨床へ包括的遺伝子発現解析を用いた糖尿病網膜症に対する治療標的の抽出 (2011)
  • Author(s): 吉田茂生,石橋達朗
  • Organizer: 第49回日本糖尿病学会
  • Place of Presentation: 福岡市
  • Year and Date: 2011-10-14
• [Presentation] Increased Expression of Periostin in Vitreous and Fibrovascular Membranes from Patients with Proliferative Diabetic Retinopathy (2011)
  • Author(s): Yoshida S, Ishikawa K, Asato R, Sassa Y, Yoshikawa H, Izuhara K, Kono T, Ishibashi T
  • Organizer: The Association for Research in Vision and Ophthalmology Annual Meeting
  • Place of Presentation: Fort Laudardale
• [Presentation] Increased Expression of Periostin in Vitreous and Fibrovascular Membranes from Patients with Proliferative Diabetic Retinopathy (2011)
  • Author(s): Yoshida, S. Ishikawa, K. Asato, R. Sassa, Y. Yoshikawa, H. Izuhara, K. Kono, T. Ishibashi, T.
  • Organizer: Association for Research in Vision and Ophthalmology
  • Place of Presentation: Fort Laudardale, USA
• [Presentation] 遺伝性眼疾患の基本知識 (2011)
  • Author(s): 吉田茂生
  • Organizer: 第4回愛知県眼科医会学術講演会(招待講演)
  • Place of Presentation: 名古屋
• [Presentation] 糖尿病合併症の克服を目指して-基礎から臨床へ 包括的遺伝子発現解析を用いた糖尿病網膜症に対する治療標的の抽出 (2011)
  • Author(s): 吉田茂生、石橋達朗
  • Organizer: 第49回日本糖尿病学会(招待講演)
  • Place of Presentation: 福岡
• [Presentation] ゲノム医科学的アプローチによる増殖性網膜硝子体疾患の責任遺伝子同定と治療への展開,第117回日本眼科学会総会
  • Author(s): 吉田 茂生
  • Organizer: 第117回日本眼科学会総会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 糖尿病網膜症の薬物治療
  • Author(s): 吉田 茂生
  • Organizer: 第11回福島糖尿病眼研究会
  • Place of Presentation: 郡山市
  • Invited
• [Presentation] ,糖尿病網膜症に対する分子標的治療
  • Author(s): 吉田 茂生
  • Organizer: 第24回やまがたDM meeting
  • Place of Presentation: 山形市
  • Invited
• [Presentation] ,Fibrovascular membranes associated with PDR: Identification of molecular targets by global gene expression profiling.
  • Author(s): Yoshida, S.
  • Organizer: The Third Kyushu-Youngnam Retina Meeting
  • Place of Presentation: Busan
  • Invited
• [Presentation] The role of M2 macrophages in the development of fibrovascular membranes in diabetic retinopathy.
  • Author(s): Yoshida, S.
  • Organizer: The Fifth Joint Meeting of Korea-China-Japan Ophthalmologists.
  • Place of Presentation: Fukuoka
• [Presentation] 網膜硝子体サンプルが教えてくれる次世代医療へのヒント.
  • Author(s): 吉田 茂生
  • Organizer: 第93回秋田県眼科集談会
  • Place of Presentation: 秋田
  • Invited
• [Remarks]
  • URL: http://www.eye.med.kyushu-u.ac.jp/