Development of new methods to prevent the progression or recover the vision in eyes of retinitis pigmentosa

2009 Fiscal Year Final Research Report

• Project/Area Number: 19209053
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Osaka University
• Principal Investigator: FUJIKADO Takashi Osaka University, 医学系研究科, 教授 (50243233)
• Co-Investigator(Kenkyū-buntansha): OHTA Jun 奈良先端科学技術大学院大学, 物質創成科学研究所, 教授 (80304161) ; OHJI Masahito 滋賀医科大学, 医学部, 教授 (90252650) ; KAMEI Motohiro 大阪大学, 医学系研究科, 准教授 (40281125) ; IKUNO Yasushi 大阪大学, 医学系研究科, 講師 (50294096) ; THUJIKAWA Motokazu 大阪大学, 医学系研究科, 助教 (70419472) ; SAKAGUCHI Hirokazu 大阪大学, 医学系研究科, 助教 (80379172) ; SAWAI Hajime 大阪大学, 医学系研究科, 准教授 (20202103)
• Project Period (FY): 2007 – 2009
• Keywords: 網膜色素変性症 / 人工視覚 / 細胞死抑制

Research Abstract

1) We made constructs of 14 kinds of human rhodopsin mutants and injected 10 of the 14 into zebrafish embryos to establish transgenic lines for each mutation. We also performed phenotype analyses and found that the numbers of rod photoreceptors decreased in K296E, R135W, Q344X, and S334X transgenic lines. These transgenic lines are useful as a model of human retinitis pigmentosa.
2) We developed a unique and novel electrode device. The device was handled easily using a vitreoretinal forceps in the vitreous cavity and was easily implanted into the optic disc with one action. The patient perceived phosphenes with electrical stimulation through each of the electrodes.

Research Products

• [Journal Article] Efficacy of suprachoroidal-transretinal stimulation in a rabbit model of retinal degeneration. (2010)
  • Author(s): Nishida K, Kamei M, Kondo M, Sakaguchi H, Suzuki M, Fujikado T, Tano Y.
  • Journal Title: Invest Ophthalmol Vis Sci 51(4) Pages: 2263-8
  • Peer Reviewed
• [Journal Article] Light-controlled retinal stimulation on rabbit using CMOS-based flexible multi-chip stimulator. (2009)
  • Author(s): Tokuda T, Takeuchi Y, Noda T, Sasagawa K, Nishida K, Kitaguchi Y, Fujikado T, Tano Y, Ohta J
  • Journal Title: Conf Proc IEEE Eng Med Biol Soc. 2009 Pages: 646-9
  • Peer Reviewed
• [Journal Article] Artificial vision by direct optic nerve electrode (AV-DONE) implantation in a blind patient with retinitis pigmentosa. (2009)
  • Author(s): Sakaguchi H, Kamei M, Fujikado T, Yonezawa E, Ozawa M, Cecilia-Gonzalez C, Ustariz-Gonzalez O, Quiroz-Mercado H, Tano Y.
  • Journal Title: J Artif Organs 12(3) Pages: 206-9
  • Peer Reviewed
• [Journal Article] 人工視覚システムの臨床応用を目指して (2009)
  • Author(s): 田野保雄, 瓶井資弘, 生野恭司, 辻川元一, 坂口裕和, 西田健太郎, 方肖雲, 杜兆江, 謝平, 不二門尚, 日下俊次, 森本壮, 中内一揚, 別所建一郎, 下條裕史, 大川賀孝, 北口善之, 福田淳, 澤井元, 三好智満, 八木哲也, 小山内実, 宋文杰, 三宅養三, 近藤峰生, 子安俊行, 坂井隆夫, 栗本幸英, 平形明人, Quiroz-MercadoHugo, Ustariz-GonzalezOrlando, Cecilia-GonzalezCarmen, 太田淳, 徳田崇, 小澤素生田野保雄, 瓶井資弘, 生野恭司, 辻川元一, 坂口裕和, 西田健太郎, 方肖雲, 杜兆江, 謝平, 不二門尚, 日下俊次, 森本壮, 中内一揚, 別所建一郎, 下條裕史, 大川賀孝, 北口善之, 福田淳, 澤井元, 三好智満, 八木哲
  • Journal Title: 日本眼科学会雑誌 113巻 Pages: 315-343
  • Peer Reviewed
• [Journal Article] Generation of a transgenic rabbit model of retinal degeneration. (2009)
  • Author(s): Kondo M, Sakai T, Komeima K, Kurimoto Y, Ueno S, Nishizawa Y, Usukura J, Fujikado T, Tano Y, Terasaki H.
  • Journal Title: Invest Ophthalmol Vis Sci. 50(3) Pages: 1371-7
  • Peer Reviewed
• [Journal Article] Multi-finger structure and pulsed-powering operation scheme for CMOS LSI-based flexible stimulator for retinal prosthesis. (2008)
  • Author(s): Tokuda T, Asano R, Hiyama K, Terasawa Y, Nishida K, Kitaguchi Y, Fujikado T, Tano Y, Ohta J.
  • Journal Title: Conf Proc IEEE Eng Med Biol Soc. 2008 Pages: 4212-5
  • Peer Reviewed
• [Journal Article] Effect of electrical stimulation on IGF-1 transcription by L-type calcium channels in cultured retinal Muller cells. (2008)
  • Author(s): Sato T, Fujikado T, Morimoto T, Matsushita K, Harada T, Tano Y.
  • Journal Title: Jpn J Ophthalmol 52(3) Pages: 217-23
  • Peer Reviewed
• [Journal Article] Direct effect of electrical stimulation on induction of brain-derived neurotrophic factor from cultured retinal Muller cells. (2008)
  • Author(s): Sato T, Fujikado T, Lee TS, Tano Y.
  • Journal Title: Invest Ophthalmol Vis Sci 49(10) Pages: 4641-6
  • Peer Reviewed
• [Journal Article] Adaptive optics fundus camera to examine localized changes in the photoreceptor layer of the fovea. (2008)
  • Author(s): Kitaguchi Y, Fujikado T, Bessho K, Sakaguchi H, Gomi F, Yamaguchi T, Nakazawa N, Mihashi T, Tano Y.
  • Journal Title: Ophthalmology 115(10) Pages: 1771-7
  • Peer Reviewed
• [Journal Article] Age at onset curves of retinitis pigmentosa. (2008)
  • Author(s): Tsujikawa M, Wada Y, Sukegawa M, Sawa M, Gomi F, Nishida K, Tano Y.
  • Journal Title: Arch Ophthalmol 126(3) Pages: 337-40
  • Peer Reviewed
• [Journal Article] In vivo stimulation on rabbit retina using CMOS LSI-based multi-chip flexible stimulator for retinal prosthesis. (2007)
  • Author(s): Tokuda T, Asano R, Sugitani S, Terasawa Y, Nunoshita M, Nakauchi K, Fujikado T, Tano Y, Ohta J.
  • Journal Title: Conf Proc IEEE Eng Med Biol Soc 2007 Pages: 5791-4
  • Peer Reviewed
• [Journal Article] Optical imaging to evaluate retinal activation by electrical currents using suprachoroidal-transretinal stimulation. (2007)
  • Author(s): Okawa Y, Fujikado T, Miyoshi T, Sawai H, Kusaka S, Mihashi T, Hirohara Y, Tano Y.
  • Journal Title: Invest Ophthalmol Vis Sci 48(10) Pages: 4777-84
  • Peer Reviewed
• [Journal Article] Transcorneal electrical stimulation promotes the survival of photoreceptors and preserves retinal function in royal college of surgeons rats. (2007)
  • Author(s): Morimoto T, Fujikado T, Choi JS, Kanda H, Miyoshi T, Fukuda Y, Tano Y.
  • Journal Title: Invest Ophthalmol Vis Sci 48(10) Pages: 4725-32
  • Peer Reviewed
• [Journal Article] Evaluation of phosphenes elicited by extraocular stimulation in normals and by suprachoroidal-transretinal stimulation in patients with retinitis pigmentosa. (2007)
  • Author(s): Fujikado T, Morimoto T, Kanda H, Kusaka S, Nakauchi K, Ozawa M, Matsushita K, Sakaguchi H, Ikuno Y, Kamei M, Tano Y
  • Journal Title: Graefes Arch Clin Exp Ophthalmol 245(10) Pages: 1411-9
  • Peer Reviewed
• [Journal Article] Laboratory investigation of microelectronics-based stimulators for large-scale suprachoroidal transretinal stimulation (STS). (2007)
  • Author(s): Ohta J, Tokuda T, Kagawa K, Sugitani S, Taniyama M, Uehara A, Terasawa Y, Nakauchi K, Fujikado T, Tano Y
  • Journal Title: J Neural Eng 4(1) Pages: 85-91
  • Peer Reviewed
• [Journal Article] Threshold suprachoroidal-transretinal stimulation current resulting in retinal damage in rabbits. (2007)
  • Author(s): Nakauchi K, Fujikado T, Kanda H, Kusaka S, Ozawa M, Sakaguchi H, Ikuno Y, Kamei M, Tano Y
  • Journal Title: J Neural Eng 4(1) Pages: 50-7
  • Peer Reviewed
• [Journal Article] Mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K) pathways differently regulate retinal pigment epithelial cell-mediated collagen gel contraction. (2006)
  • Author(s): Bando H, Ikuno Y, Hori Y, Sayanagi K, Tano Y
  • Journal Title: Exp Eye Res 82 Pages: 529-37
  • Peer Reviewed
• [Presentation] Photoreceptor Changes at One-Year Follow-Up of Titanium:Sapphire Laser Retinal Injury Observed With Flood-Illumination Adaptive Optics Fundus Camera. (2009)
  • Author(s): Kitaguchi Y., Fujikado T., Kusaka S., Yamaguchi T., Hirohara Y., Mihashi T., Maeda N., Tano Y.
  • Organizer: 2009 ARVO Annual meeting
  • Place of Presentation: Fort Lauderdale
  • Year and Date: 20090503-20090507
• [Presentation] Effect of Transcorneal Electrical Stimulation(tes) in Patients With Traumatic Optic Neuropathy(ton) (2009)
  • Author(s): Shimojyo H., Fujikado T., Morimoto T., Okawa Y., Matsushita K., Kitaguti Y., Tano Y.
  • Organizer: 2009 ARVO Annual meeting
  • Place of Presentation: Fort Lauderdale
  • Year and Date: 20090503-20090507
• [Presentation] 脈絡膜上経網膜刺激において大脳皮質誘発電位に影響を与える因子. (2009)
  • Author(s): 西田健太郎、瓶井資弘、坂口裕和、北口善之、不二門尚、田野保雄
  • Organizer: 第113回日本眼科学会総会
  • Place of Presentation: 東京
  • Year and Date: 20090416-20090419
• [Presentation] 網膜色素変性モデルゼブラフィッシュにおける視細胞死の検討 (2009)
  • Author(s): 中尾武史、松村永和、辻川元一、田野保雄
  • Organizer: 第113回日本眼科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-04-16
• [Presentation] Contribution of Retinal Ganglion Cells to Intrinsic Signals in Retinal Optical Imaging by Trans-Corneal Electrical Stimulation or by Light Stimulation. (2008)
  • Author(s): Fujikado T., Okawa Y., Miyoshi T., Hirohara Y., Mihashi T., Tano Y.
  • Organizer: 2008 ARVO Annual meeting
  • Place of Presentation: Fort Lauderdale
  • Year and Date: 20080427-20080501
• [Presentation] Reduced Photoreceptor Thickness Causes Blur of Photoreceptor Mosaic in the Image by Flood-illumination Adaptive Optics Fundus Camera. (2008)
  • Author(s): Kitaguchi Y., Fujikado T., Bessho K., Yamaguchi T., Nakazawa N., Hirohara Y., Mihashi T., Maeda N., Tano Y.
  • Organizer: 2008 ARVO Annual meeting
  • Place of Presentation: Fort Lauderdale
  • Year and Date: 20080427-20080501
• [Presentation] Repeatability of Intrinsic Optical Imaging of the Retina's Response to Optical and Electric Stimuli. (2008)
  • Author(s): Mihashi T., Hirohara Y., Okawa Y., Miyoshi T., Fujikado T.
  • Organizer: 2008 ARVO Annual meeting
  • Place of Presentation: Fort Lauderdale
  • Year and Date: 20080427-20080501
• [Presentation] Suprachoridal-Transretinal Stimulation (STS) Generates EEP in a Middle-Sized Animal Model of Retinal Degeneration. (2008)
  • Author(s): Nishida K., Kamei M., Kondo M., Sakai T., Z. Du Y., Kitaguchi Y., Nakauchi K., Sakaguchi H., Fujikado T., Tano Y.
  • Organizer: 2008 ARVO Annual meeting
  • Place of Presentation: Fort Lauderdale
  • Year and Date: 20080427-20080501
• [Presentation] Artificial Vision by Direct Optic Nerve Electrode (AV-DONE) for a Blind Patient With Retinitis Pigmentosa. (2008)
  • Author(s): Sakaguchi H., Kamei M., Fujikado T., Yonezawa E., Ozawa M., Cecilia-Gonzalez C., Ustariz-Gonzalez O., Quiroz-Mercado H., Tano Y.
  • Organizer: 2008 ARVO Annual meeting
  • Place of Presentation: Fort Lauderdale
  • Year and Date: 20080427-20080501
• [Presentation] 補償光学眼底カメラの画像に残存収差および網膜形態が及ぼす影響 (2008)
  • Author(s): 北口善之、不二門尚、別所建一郎、山口達夫、中澤直樹、広原陽子、三橋俊文、前田直之、田野保雄
  • Organizer: 第112回日本眼科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 20080417-20080420
• [Presentation] ロドプシントランスジェニックウサギ作成の試み (2008)
  • Author(s): 近藤峰生、坂井隆夫、米今敬一、栗本幸英、子安俊行、宮田健太郎、西沢祐治、臼倉治郎、不二門尚、田野保雄、寺崎浩子
  • Organizer: 第112回日本眼科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 20080417-20080420
• [Presentation] 外傷性視神経症(TON)に対する経角膜電気刺激を用いた神経保護治療の検討. (2008)
  • Author(s): 下條裕史、不二門尚、森本壮、松下賢治、大川賀孝、北口善之、田野保雄
  • Organizer: 第112回日本眼科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 20080417-20080420
• [Presentation] 中型動物における視細胞障害モデルの作成 (2008)
  • Author(s): 西田健太郎、瓶井資弘、坂口裕和、近藤峰生、不二門尚、田野保雄
  • Organizer: 第112回日本眼科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 20080417-20080420
• [Presentation] Functional Imaging (2008)
  • Author(s): 不二門尚
  • Organizer: 第112回日本眼科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 20080417-20080420
• [Presentation] Adaptive Optics Retinal Imaging in Rabbit Eyes (2007)
  • Author(s): Kitaguchi Y., Fujikado T., Bessho K., Yamaguchi T., Nakazawa N, Hirohara Y., Mihashi T., Maeda N., Tano Y.
  • Organizer: 2007 ARVO Annual meeting
  • Place of Presentation: Fort Lauderdale
  • Year and Date: 20070506-20070510
• [Presentation] Contribution of Retinal Ganglion Cell Activity to Intrinsic Signals (2007)
  • Author(s): Okawa Y., Fujikado T., Miyoshi T., Hirohara Y., Mihashi T., Tano Y.
  • Organizer: 2007 ARVO Annual meeting
  • Place of Presentation: Fort Lauderdale
  • Year and Date: 20070506-20070510
• [Presentation] Artificial Vision by Direct Optic Nerve Electrode (AV-DONE) for a Patient with Retinitis Pigmentosa. (2007)
  • Author(s): Sakaguchi H., Yonezawa E., Kanda H., Ozawa M., Kamei M., Fujikado T., Ustariz-Gonzalez O., Solis-Vivanco A., Quiroz-Mercado H., Tano Y.
  • Organizer: 2007 ARVO Annual meeting
  • Place of Presentation: Fort Lauderdale
  • Year and Date: 20070506-20070510
• [Presentation] The Effect of Electrical Stimulation on Cultured Retinal Muller Cells. (2007)
  • Author(s): Sato T., Fujikado T., Matsushita K., Morimoto T., Kanda H., Harada T., Kusaka S., Tano Y.
  • Organizer: 2007 ARVO Annual meeting
  • Place of Presentation: Fort Lauderdale
  • Year and Date: 20070506-20070510
• [Presentation] Artificial Vision by Direct Optic Nerve Electrode for Patients with Retinitis Pigmentosa. (2007)
  • Author(s): Sakaguchi H., Yonezawa E., Kanda H., Ozawa M., Kamei M., Fujikado T., Ustariz-Gonzalez O., Solis-Vivanco A., Quiroz-Mercado H., Tano Y.
  • Organizer: 2007 ARVO Annual meeting
  • Place of Presentation: Fort Lauderdale
  • Year and Date: 20070506-20070510
• [Presentation] 網膜神経節細胞に起因する内因性信号 (2007)
  • Author(s): 大川賀孝, 不二門尚, 三好智満, 広原陽子, 三橋俊文, 田野保雄
  • Organizer: 第111回日本眼科学会総会
  • Place of Presentation: 大阪
  • Year and Date: 20070419-20070422
• [Presentation] 有色家兎を用いた、補償光学眼底カメラの機能解析. (2007)
  • Author(s): 北口善之, 不二門尚, 別所健一郎, 山口達夫, 中澤直樹, 広原陽子, 三橋俊文, 前田直之, 田野保雄
  • Organizer: 第111回日本眼科学会総会
  • Place of Presentation: 大阪
  • Year and Date: 20070419-20070422
• [Presentation] 培養Muller細胞に対する電気刺激の生理的、機能的影響 (2007)
  • Author(s): 佐藤達彦, 不二門尚, 松下賢治, 森本壮, 神田寛行, 田野保雄
  • Organizer: 第111回日本眼科学会総会
  • Place of Presentation: 大阪
  • Year and Date: 20070419-20070422
• [Presentation] 瞳孔反応によるTON患者に対する経角膜電気刺激治療の効果判定 (2007)
  • Author(s): 松下賢治, 不二門尚, 下條裕史, 森本壮, 北口善之, 大川賀孝, 田野保雄
  • Organizer: 第111回日本眼科学会総会
  • Place of Presentation: 大阪
  • Year and Date: 20070419-20070422
• [Presentation] 経角膜電気刺激の損傷網膜神経節細胞に対する生存促進効果の刺激条件による変化. (2007)
  • Author(s): 森本壮, 不二門尚, 三好智満, 田野保雄
  • Organizer: 第111回日本眼科学会総会
  • Place of Presentation: 大阪
  • Year and Date: 20070419-20070422
• [Patent(Industrial Property Rights)] 特許権 (2011)
  • Inventor(s): 瓶井資弘、坂口裕和
  • Industrial Property Rights Holder: (株)ニデック
  • Industrial Property Number: 特願・2010-031671
  • Filing Date: 2011-02-16