Generation of nitric oxide synthase transgenic mice and analysis of their visual function

• Project/Area Number: 20592074
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Nagoya University
• Principal Investigator: KOMEIMA Keiichi Nagoya University, 大学院・医学系研究科, 助教 (40362256)
• Co-Investigator(Kenkyū-buntansha): KONDO Mineo 名古屋大学, 大学院・医学系研究科, 准教授 (80303642) ; TERASAKI Hiroko 名古屋大学, 大学院・医学系研究科, 教授 (40207478)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2009: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2008: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 一酸化窒素(NO) / 誘導型一酸化窒素合成酵素(iNOS) / 網膜色素上皮細胞 / トランスジェニックマウス / 酸化・ニトロ化ストレス / VMD2プロモーター / 加齢黄斑変性 / 網膜色素変性症

Research Abstract

We generated 5 lines of inducible nitric oxide synthase transgenic mice. Fundus examination revealed retinal drusen in 3 lines of transgenic mice. These results indicated that nitric oxide overexpressed in the outer layer of retinas caused oxidative stress and degenerative change in mouse retinas as is seen in the patients of age-related macular degeneration.

Research Products

• [Journal Article] Regulation of pathologic retinal angiogenesis in mice and inhibition of VEGF-VEGFR2 binding by soluble heparan sulfate. (2010)
  • Author(s): Nishiguchi KM, Kataoka K, Kachi S, Komeima K, Terasaki H.
  • Journal Title: PLoS One. 55
  • Peer Reviewed
• [Journal Article] Inner Retinal Cleavage Associated With Idiopathic Epiretinal Membrane. (2010)
  • Author(s): Komeima, K, Ito Y, Nakamura, M, Terasaki H.
  • Journal Title: Retin Cases Brief Rep. 4 Pages: 132-134
  • Peer Reviewed
• [Journal Article] Regulation of pathologic retinal angiogenesis in mice and inhibition of VEGF-VEGFR2 binding by soluble heparan sulfate. (2010)
  • Author(s): Nishiguchi KM, Kataoka K, Kachi S, Komeima K, Terasaki H.
  • Journal Title: PLoS One. Volume: 5
  • Peer Reviewed
• [Journal Article] Inner Retinal Cleavage Associated With Idiopathic Epiretinal Membrane (2010)
  • Author(s): Komeima. K, Ito Y, Nakamura, M, Terasaki H.
  • Journal Title: Retin Cases Brief Rep. Volume: 4 Pages: 132-134
  • Peer Reviewed
• [Journal Article] Supernormal ERG oscillatory potentials in transgenic rabbit with rhodopsin P347L mutation and retinal degeneration. (2009)
  • Author(s): Sakai T, Kondo M, Ueno S, Koyasu T, Komeima K, Terasaki H.
  • Journal Title: Invest Ophthalmol Vis Sci. 50 Pages: 4402-4409
  • Peer Reviewed
• [Journal Article] Increased expression of catalase and superoxide dismutase 2 reduces cone cell death in retinitis pigmentosa. (2009)
  • Author(s): Usui S, Komeima K, Lee SY, Jo YJ, Ueno S, Rogers BS, Wu Z, Shen J, Lu L, Oveson BC, Rabinovitch PS, Campochiaro PA.
  • Journal Title: Mol Ther. 17 Pages: 778-786
  • Peer Reviewed
• [Journal Article] Increased expression of glutathione peroxidase 4 strongly protects retina from oxidative damage. (2009)
  • Author(s): Lu L, Oveson BC, Jo YJ, Lauer TW, Usui S, Komeima K, Xie B, Campochiaro PA.
  • Journal Title: Antioxid Redox Signal. 11 Pages: 715-724
  • Peer Reviewed
• [Journal Article] Supernormal ERG oscillatory potentials in transgenic rabbit with rhodo psin P347L mutation and retinal degeneration. (2009)
  • Author(s): Sakai T, et al.
  • Journal Title: Invest Ophthalmol Vis Sci. 50 Pages: 4402-9
  • Peer Reviewed
• [Journal Article] Increased expression of glutathione peroxidase 4 strongly protects retina from oxidative damage. (2009)
  • Author(s): Lu L, et al.
  • Journal Title: Antioxid Redox Signal. 11 Pages: 715-24
  • Peer Reviewed
• [Journal Article] Increased expression of catalase and superoxide dismutase 2 reduces co ne cell death in retinitis pigmentosa. (2009)
  • Author(s): Usui S, et al.
  • Journal Title: Mol Ther. 17 Pages: 778-86
  • Peer Reviewed
• [Journal Article] 一酸化窒素と網膜疾患 (2009)
  • Author(s): 米今敬一
  • Journal Title: 臨床眼科 63 Pages: 9-14
  • NAID: 40016440950
• [Journal Article] Generation of a Transgenic Rabbit Model of Retinal Degeneration. (2009)
  • Author(s): Kondo M, et al.
  • Journal Title: Invest Ophthalmol Vis Sci. 50 Pages: 1371-1377
  • Peer Reviewed
• [Journal Article] Increased Expression of Glutathione Peroxidase 4 Strongly Protects Retina from Oxidative Damage. (2008)
  • Author(s): Lu L, et al.
  • Journal Title: Antioxid Redox Signal. (In Press)
  • Peer Reviewed
• [Journal Article] Blockade of neuronal nitric oxide synthase reduces cone cell death in a model of retinitis pismentosa. (2008)
  • Author(s): Komeima K, et al.
  • Journal Title: Free Radic Biol Med. 45 Pages: 905-912
  • Peer Reviewed
• [Presentation] Girdin phosphorylation at serine-1416 by Akt/PkB promotes postneonatal angiogenesis and ischemic neovascularization in the retina. (2010)
  • Author(s): Takanori Ito, Keiichi Komeima, Tetsuhiro Yasuma, et al.
  • Organizer: ARVO Meeting
  • Place of Presentation: Ft.Lauderdale, USA
  • Year and Date: 2010-05-02
• [Presentation] Girdin phosphorylation at serine-1416 by Akt/PkB promotes postneonatal angiogenesis and ischemic neovascularization in the retina (2010)
  • Author(s): Takanori Ito, Keiichi Komeima, Tetsuhiro Yasuma, et al.
  • Organizer: ARVO Meeting 2010
  • Place of Presentation: Ft.Lauderdale, USA
  • Year and Date: 2010-05-02
• [Presentation] The functional role of Akt substrate Girdin in retinal angiogenesis (2010)
  • Author(s): Keiichi Komeima
  • Organizer: 第114回日本眼科学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2010-04-16
• [Presentation] The functional role of Akt substrate Girdin in retinal angiogenesis (2010)
  • Author(s): 米今敬一
  • Organizer: 第114回日本眼科学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-04-15
• [Presentation] 網膜静脈閉塞の病態生理に対する考察 (2009)
  • Author(s): 米今敬一
  • Organizer: 第63回日本臨床眼科学会
  • Place of Presentation: 福岡
  • Year and Date: 2009-10-09
• [Presentation] 網膜静脈閉塞の病態生理に対する考察 (2009)
  • Author(s): 米今敬一
  • Organizer: 第63回 日本臨床眼科学会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2009-10-09
• [Presentation] 網膜色素変性症と一酸化窒素 (2008)
  • Author(s): 米今敬一
  • Organizer: 第47回日本網膜硝子体学会総会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2008-11-28