reseatch for the neuro-protection ofretina and optic nerve by trans-corneal electrical stimulation

• Project/Area Number: 18591918
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Osaka University
• Principal Investigator: FUJIKADO Takashi Osaka University, Graduate School of Medicine, Professor (50243233)
• Co-Investigator(Kenkyū-buntansha): KUSAKA Shumji Osaka University, Graduate School of Medicine, Associate Professor (60260387) ; MATSUSHITA Kenji Osaka University, Graduate School of Medicine, Assistant Professor (40437405) ; MIYOSHI Tomomitsu Osaka University, Graduate School of Medicine, Assistant Professor (70314309) ; 大鳥 安正 大阪大学, 医学系研究科, 講師 (40303953)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: Neuroprotection / Trans-corneal electrical stimulation / Traumatic Optic Neuropathy / Ischemic Optic Neuropathy / IGF-1 / 電気刺激 / 神経栄養因子 / 視神経症 / 緑内障

Research Abstract

(1). Molecular mechanism of neroprotection for the retina and optic nerve by trans-corneal electrical stimulation.
Based on our previous report that trans-corneal electrical stimulation to the retina prevented neuronal death of retinal ganglion cells with up-regulation of Insulin-like growth factor 1(IGF1), we studied if IGF-1 was up-regulated by electrical stimulation to the cultured Mueller cells using RT-PCR. The result was that the mRNA of IGF-1 significantly increased if the mRNA was extracted just after the cessation of 30 minutes electrical stimulation. The Ca++ imaging showed that intracellular Ca++ concentration increased just after the start of electrical stimulation, reached 1.5 fold at 30minutes. The increase of Ca++ concentration was completely blocked by the application of Nifedipine, an L-type Ca++ channel blocker. These results indicated that the electrical stimulation promotes the transcription of IGF-1 gene and this phenomenon is related to the increase of intracellular concentration of Ca++ through the L-type Ca++ channel.
(2). Clinical investigation of trans-corneal electrical stimulation to the optic neuropathy
We investigated the effect of trans-corneal electrical stimulation (TcES) to the eye with ischemic optic neumpathy (ION) or traumatic optic neumpathy (TON). Consecutive chromic patients with ION (20 eyes) and TON (10 eyes) who visited Osaka University hospital between June 2003 and May 2006 in which TcES was applied with an interval of 6 to 8 weeks were examined. The increase of visual acuity greater than 0.3 Log MAR unit were observed in 6 eyes (30%) of ION and 5 eyes (50%) of TON. No patient decreased vision more than 0.3 Log MAR unit. These data suggests that TcES is effecive in some patients with ION and TON.

Research Products

• [Journal Article] The Effbct of Electrical Stimulation on IGF-1 Transcription via L-type Calcium Channel 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 (In press)
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] The Effect of Electrical Stimulation on IGF-1 Transcription via L-type Calcium Channel in Cultured Retinal Muller Cells (2008)
  • Author(s): Sato, T
  • Journal Title: Jpn J Ophthalmol (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [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 Pages: 4725-4732
  • Description: 「研究成果報告書概要(和文)」より
  • 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 Pages: 4777-4784
  • Description: 「研究成果報告書概要(和文)」より
  • 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, Matsushit K, Sakaguchi H, Ikuno Y, Kamei M, Tano Y,
  • Journal Title: Graefes Arch Clin Exp Ophthalmol 245 Pages: 1411-1419
  • Description: 「研究成果報告書概要(和文)」より
  • 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
  • Journal Title: Invest Ophthalmol Vis Sci 48 Pages: 4725-4732
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Optical Imaging to Evaluate Retinal Activation by Electrical Currents using Suprachoroidal-Transretinal Stimulation (2007)
  • Author(s): Okawa, Y
  • Journal Title: Invest Ophthalmol Vis Sci 48 Pages: 4777-4784
  • Description: 「研究成果報告書概要(欧文)」より
• [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
  • Journal Title: Graefes Arch Clin Exp Ophthalmol 245 Pages: 1411-1419
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Vision of a Newcomer In Artificial Sight Basic Research, Biomedical Engineering, and Clinical Advances Humayun MS, Weiland JD, Chader G and Greenbaum E eds (2007)
  • Author(s): Fujikado, T, Sawai, H, Tano, Y Artificial Vision
  • Journal Title: Springer 14
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Optical Imaging to Evaluate Retinal Activation by Electrical Curents 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 Pages: 4777-4784
  • Peer Reviewed
• [Journal Article] Effect of Transcorneal Electrical Stimulation in Patients with Nonarteritic Ischemic Optic Neuropathy and Traumatic Optic Neuropathy (2006)
  • Author(s): Fujikado T, Morimoto T, Matsushita K, Shimojo H, Okawa Y, Tano Y.
  • Journal Title: Jpn J Ophthalmol. 50(3) Pages: 266-273
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Evaluation of residual retinal function by pupillary constrictions and phosphenes using transcorneal electrical stimulation in patients with retinal degeneration. (2006)
  • Author(s): Morimoto T, Fukui T, Matsushita K, Okawa Y, Shimojyo H, Kusaka S, Tano Y, Fujikado T.
  • Journal Title: Graefes Arch Clin Exp Ophthalmol, 244(10) Pages: 1283-1292
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Effect of Transcorneal Electrical Stimulation in Patients with Nonarteritic Ischemic Optic Neuropathy and Traumatic Optic Neuropathy (2006)
  • Author(s): Fujikado, T
  • Journal Title: Jpn J Ophthalmol 50(3) Pages: 266-273
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Evaluation of Residual Retinal Function by Pupillary Constrictions and Phosphenes using Transcorneal Electrical Stimulation in Patients with Retinal Degeneration (2006)
  • Author(s): Morimoto, T
  • Journal Title: Graefes Arch Clin Exp Ophthalmol 244(10) Pages: 1283-1292
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Evaluation of residual retinal function by pupillary constrictions and phosphenes using transcorneal electrical stimulation in patients with retinal degeneration. (2006)
  • Author(s): Morimoto T, Fukui T, Matsushita K, Okawa Y, Shimojyo H, Kusaka S, Tano Y, Fujikado T.
  • Journal Title: Graefes Arch Clin Exp Ophthalmol 244(10) Pages: 1283-1292
• [Journal Article] Null ABCA4 Gene Mutations Found in Japanese Patients with Panretinal Degeneration (2006)
  • Author(s): Fukui T, Fujikado T, Tsujikawa M, Okada M, Yamamoto S, Tano Y.
  • Journal Title: Jpn J Ophthalmol. 50(2) Pages: 179-181
• [Journal Article] Wavefront Analysis of Eye with Monocular Diplopia and Cortical Cataract (2006)
  • Author(s): Fujikado T, Shimojyo H, Hosohata J, Yoko Hirohara Y, Mihashi T, Maeda N, Tano Y
  • Journal Title: Am J Ophthalmol 141(6) Pages: 1138-1140
• [Journal Article] Electrophysiological and histological studies of chronically implanted intrapapillary microelectrodes in rabbit eyes. (2006)
  • Author(s): Fang X, Sakaguchi H, Fujikado T, Osanai M, Ikuno Y, Kamei M, Ohji M, Yagi T, Tano Y.
  • Journal Title: Graefes Arch Clin Exp Ophthalmol. 244(3) Pages: 364-375
• [Journal Article] Threshold suprachoroidal-transretinal stimulation current resulting in retinal damage in rabbit (2006)
  • Author(s): Nakauchi K, Fujikado T, Kanda H, Kusaka S, Ozawa M, T, Sakaguchi H, Ikuno Y, Kamei M, Tano Y.
  • Journal Title: J Neural Eng. 3 Pages: 1-8
• [Presentation] Contribution of Retinal Ganglion Cell Activity to Intrinsic Signals (2007)
  • Author(s): Y. Okawa, T. Fujikado, T. Miyoshi, T. Mihashi, Y. Hirohara, Y. Tano
  • Organizer: アメリカ視覚眼科学会(ARVO)
  • Place of Presentation: Fort Lauderdale, FL
  • Year and Date: 2007-05-09
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Contribution of Retinal Ganglion Cell Activity to Intrinsic Signals (2007)
  • Author(s): Y., Okawa, T., Fujikado, T., Miyoshi, T., Mihashi, Y., Hirohara, Y., Tano
  • Organizer: ARVO meeting
  • Place of Presentation: Florida, USA
  • Year and Date: 2007-05-09
  • Description: 「研究成果報告書概要(欧文)」より
• [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, Tano Y
  • Organizer: アメリカ視覚眼科学会(ARVO)
  • Place of Presentation: Fort Lauderdale, FL
  • Year and Date: 2007-05-08
  • Description: 「研究成果報告書概要(和文)」より
• [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, Tano, Y
  • Organizer: ARVO meeting
  • Place of Presentation: Florida, USA
  • Year and Date: 2007-05-08
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] Artificial Vision: Vision of a Newcomer In Artificial Sight Basic Research, Biomedical Engineering, and Clinical Advances Humayun MS, Weiland JD, Chader G and Greenbaum E eds (2007)
  • Author(s): Fujikado T, Sawai H and Tano Y.
  • Total Pages: 14
  • Publisher: Springer
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Artificial Vision : Vision of a Newcomer. In Artificial Sight, M. S. Humayun, J. D. Weiland, G. Chader and E. Greenbaum (Editors) (2007)
  • Author(s): Fujikado T, Sawai H, Tano Y
  • Publisher: Springer-New York(in press)