加齢黄斑変性における脈絡膜新生血管発症機序の解明(AβとHtrA1の関与)

• Project/Area Number: 19890070
• Research Category: Grant-in-Aid for Young Scientists (Start-up)
• Allocation Type: Single-year Grants
• Research Field: Ophthalmology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: YOSHIDA Takeshi Tokyo Medical and Dental University, 医学部附属病院, 助教 (30451941)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,085,000 (Direct Cost: ¥2,680,000、Indirect Cost: ¥405,000); Fiscal Year 2008: ¥1,755,000 (Direct Cost: ¥1,350,000、Indirect Cost: ¥405,000); Fiscal Year 2007: ¥1,330,000 (Direct Cost: ¥1,330,000)
• Keywords: 加齢黄斑変性 / アミロイドβ / 老化 / 脈絡膜新生血管 / Amyloid beta / Htral / MMP / 遺伝子 / 生体分子

Research Abstract

AβはRPEに対しHtra1とMMP2という二つの重要なプロテアーゼの発現を亢進させることが明らかになった。さらにMMP2発現上昇の過程として、AβはMMP14の重要なtranscriptional factorであるNFkBを活性化させ、このNFkBの活性化がMMP14発現を亢進させる可能性が示唆された。このMMP14の発現亢進が引き続きMMP2を活性型へと導くことで、Bruch膜の構造変化を引き起こす可能性があると予想される。AMDにおける脈絡膜新生血管発生の過程の中でAβのBruch膜への影響は重要なステップと考えられ、AMDにおける予防治療のアプローチを考慮する際に重要であると思われる。

Research Products

• [Journal Article] Intravitreal bevacizumab onmyopic choroidal neovascularization thatwas refractory to or had recurred afterphotodynamic therapy (2009)
  • Author(s): Hayashi K, Ohno-Matsui K, Shimada N, Moriyama M, Hara W, Yoshida T, Tokoro T, Mochizuki M
  • Journal Title: Graefes Arch Clin Exp Ophthalmol 247(5) Pages: 609-18
  • Peer Reviewed
• [Journal Article] Altered function of factor I caused by amyloid beta : implication for pathogenesis of age-related macular degeneration from Drusen (2008)
  • Author(s): Wang J, Ohno-Matsui K, Yoshida T, Kojima A, Shimada N, Nakahama K, Safranova O, Iwata N, Saido TC, Mochizuki M, Morita I
  • Journal Title: J Immunol 181(1) Pages: 712-20
  • Peer Reviewed
• [Journal Article] Progression from macular retinoschisis to retinal detachment in highly myopic eyes is associated with outer lamellar hole for mation (2008)
  • Author(s): Shimada N, Ohno-Matsui K, Yoshida T, Sugamoto Y, Tokoro T, Mochizuki M
  • Journal Title: Br J Ophthalmol 92(6) Pages: 762-4
  • Peer Reviewed
• [Journal Article] Clinical characteristics of posterior staphyloma in eyes with pathologic myopia (2008)
  • Author(s): Hsiang HW, Ohno-Matsui K, Shimada N, Hayashi K, Moriyama M, Yoshida T, Tokoro T, Mochizuki M
  • Journal Title: Am J Ophthalmol 146(1) Pages: 102-110
  • Peer Reviewed
• [Journal Article] Photodynamic therapy with verteporfin for choroidal neovascularization of pathologic myopia in Japanese patients : comparison with nontreated controls (2008)
  • Author(s): Hayashi K, Ohno-Matsui K, Teramukai S, Shimada N, Moriyama M, Hara W, Yoshida T, Tokoro T, Mochizuki M
  • Journal Title: Am J Ophthalmol 145(3) Pages: 518-526
  • Peer Reviewed
• [Journal Article] Development of macular hole and macular retinoschisis in eyes with myopic choroidal neovascularization (2008)
  • Author(s): Shimada N, Ohno-Matsui K, Yoshida T, Futagami S, Tokoro T, Mochizuki M
  • Journal Title: Am J Ophthalmol 145(1) Pages: 155-161
  • Peer Reviewed
• [Journal Article] Detection of paravascular lamellar holes and other paravascular abnormalities by optical coherence tomography in eyes with high myopia (2008)
  • Author(s): Shimada N, Ohno-Matsui K, Nishimuta A, Moriyama M, Yoshida T, Tokoro T, Mochizuki M
  • Journal Title: Ophthalmology 115(4) Pages: 708-17
  • Peer Reviewed
• [Journal Article] Altered function of factor I caused by amyloid beta : implication for pathogenesis of a ge-related macular degeneration from Drusen. (2008)
  • Author(s): Wang J, Ohno -Matsui K, Yoshida T, Nakahama K, Iwata N, Saido TC, Mochizuki M, MoritaI
  • Journal Title: Journal of Immunol ogy 247 Pages: 609-18
  • Peer Reviewed
• [Journal Article] Development of macular hole and macular retinoschisis in eyes with myopic choroidal neovascularization. (2008)
  • Author(s): Shimada N, Ohno-Matsui K, Yoshida T, Tokoro T, Mochizuki M.
  • Journal Title: Am J Ophthalmol. 145 Pages: 155-161
  • Peer Reviewed
• [Journal Article] Clinical Characteristics of Posterior Staphyloma in Eyes with Pathologic Myopia. (2008)
  • Author(s): Hsiang HW, Ohno-Matsui K, Yoshida T, Tokoro T, Mochizuki M.
  • Journal Title: Am J Ophthalmol. (In press)
  • Peer Reviewed
• [Journal Article] Detection of paravascular lamellar holes and other paravascular abnormalities by optical coherence tomography in eyes with high myopia. (2008)
  • Author(s): Shimada N, Ohno-Matsui K, Yoshida T, Tokoro T, Mochizuki M.
  • Journal Title: Ophthalmology 115 Pages: 708-17
  • Peer Reviewed
• [Presentation] 近視性脈絡膜新生血管タイプ別による自然経過群とPDT群の予後の比較検討 (2008)
  • Author(s): 吉田武史, 大野京子, 島田典明, 林憲吾, 森山無価, 小島有里子, 安済健次郎, 林和歌子, 末吉慎一, 所敬, 望月學
  • Organizer: 第47回網膜硝子体学会
  • Place of Presentation: 京都
  • Year and Date: 2008-11-28
• [Presentation] 近視性脈絡膜新生血管の病型分類と自然経過 (2008)
  • Author(s): 吉田武史, 大野京子, 島田典明, 小島有里子, 森山無価, 林憲吾, 黄威翔, 所敬, 望月學
  • Organizer: 第62回日本臨床眼科学会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-24
• [Presentation] Correlation with the subtypes and the long-term visual outcome of myopic choroidal neovascularization (2008)
  • Author(s): T Yoshida, K Ohno-Matsui, N Shimada, A Kojima, M Moriyama, K Hayashi, T Tokoro, M Mochizuki
  • Organizer: World Ophthalmology Congress 2008 in Hongkong
  • Year and Date: 2008-07-01
• [Presentation] Amyloid-b Regulates the Gene Expression Profile of Matrix Metalloproteinases in Human Retinal Pigment Epithelial Cells (2008)
  • Author(s): T. Yoshida, K. Ohno-Matsui, J. Wang, N. Shimada, I. Morita, M. Mochizuki
  • Organizer: Annual meeting of ARVO in Fort Lauderdale FL
  • Place of Presentation: USA
  • Year and Date: 2008-04-27
• [Presentation] Reduced Retinal and Choroidal Neovascularization in Cathepsin L Gene-Deficient Mice (2008)
  • Author(s): N. Shimada, K. Ohno-Matsui, J. Wang, T. Yoshida, M. Mochizuki, I. Morita
  • Organizer: Annual meeting of ARVO in Fort Lauderdale FL
  • Place of Presentation: USA
  • Year and Date: 2008-04-27
• [Presentation] Amyloid-β regulates the gene expression profile of Matrix Metalloproteinases in human retinal pigment epithelial cells. (2008)
  • Author(s): T. Yoshida K. Ohno-Matsui, J. Wang, N. Shimada, I. Morita, M. Mochizuki
  • Organizer: The Association for Reserch in Vision and Ophthalmology 2008
  • Place of Presentation: アメリカフロリダ州フォートローダーデール市コンベンションセンター
  • Year and Date: 2008-04-27
• [Presentation] ヒト網膜色素上皮細胞におけるamyloidβ負荷時のMMP関連因子の遺伝子発現変化 (2008)
  • Author(s): 吉田武史、大野京子、王紀英、島田典明、森田育男、望月學
  • Organizer: 第112回眼科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2008-04-18
• [Presentation] ヒト網膜色素上皮細胞におけるamyloid 6負荷時のMMP関連因子の遺伝子発現変化 (2008)
  • Author(s): 吉田武史
  • Organizer: 第112回眼科学会総会
  • Place of Presentation: 横浜パシフイコ
  • Year and Date: 2008-04-18
• [Presentation] 近視性脈絡膜新生血管の病態と自然経過 (2008)
  • Author(s): 吉田武史
  • Organizer: 第112回眼科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2008-04-17
• [Presentation] ヒト網膜色素上皮細胞におけるamyloidβ負荷時のMMP関連因子の遺伝子発現変化 (2008)
  • Author(s): 吉田武史、大野京子、王 紀英、島田典明、森田育男、望月 學
  • Organizer: 日本眼科学会総会
  • Place of Presentation: 横浜市 パシフィコ横浜
  • Year and Date: 2008-04-17