Role of aquaporin in retinal and optic nerve degenerative disorders

• Project/Area Number: 26462661
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kobe University
• Principal Investigator: NAKAMURA Makoto 神戸大学, 医学研究科, 教授 (80273788)
• Co-Investigator(Kenkyū-buntansha): 山田 裕子 神戸大学, 医学研究科, 講師 (00359861) ; 金森 章泰 神戸大学, 医学研究科, 非常勤講師 (10444572) ; 三木 明子 神戸大学, 医学部附属病院, 助教 (10726988)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 視神経脊髄炎 / 緑内障 / 網膜神経節細胞 / アクアポリン / ヒト化免疫グロブリン / 光干渉断層計 / アクアポリン４ / 難治視神経疾患 / 乳酸 / アポトーシス

Outline of Final Research Achievements

An experimental neuromyelitis optica (NMO) model was established by exposing the rat optic nerve to sera from patients with anti-aquaporin 4 (AQP4) antibody-positive optic neuritis. Intravenous humanized immunogloblin G substantilly reduced the retinal ganglion cell (RGC) death. We demonstrated that the way how the AQP4 antibody positive optic neuritis damages the retinal tissue was different from the AQP4 antibody negative cases. We showed lacate transport through aquaporin 9 channel to be critical for the RGC survival.

Research Products

• [Journal Article] Impact of the anti-aquaporin-4 autoantibody on inner retinal structure, function and structure-function associations in Japanese patients with optic neuritis (2017)
  • Author(s): Matsumoto Y, Mori S, Ueda K, Kurimoto T, Kanamori A, Yamada Y, Nakashima I, Nakamura M
  • Journal Title: PLoS One Volume: 12 Issue: 2 Pages: e0171880-e0171880
  • DOI: 10.1371/journal.pone.0171880
  • NAID: 120005997131
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Rescue effects of intravenous immunoglobulin on optic nerve degeneration in a rat model of neuromyelitis optica (2016)
  • Author(s): Nobuyoshi S, Kanamori A, Matsumoto Y, Nakamura M
  • Journal Title: Jpn J Ophthalmol Volume: 60 Issue: 5 Pages: 419-423
  • DOI: 10.1007/s10384-016-0454-0
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Aquaporin 9 expression is required for l-lactate to maintain retinal neuronal survival (2015)
  • Author(s): Akashi A, Miki A, Kanamori A, Nakamura M
  • Journal Title: Neurosci Lett. Volume: 589 Pages: 185-90
  • DOI: 10.1016/j.neulet.2015.01.063
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Reproducibility in the global indices for multifocal visual evoked potentials and Humphrey visual fields in controls and glaucomatous eyes within a 2-year period (2015)
  • Author(s): Yukako Inoue, Kei Kato, Seiko Kamata, Kumiko Ishikawa, Makoto Nakamura
  • Journal Title: Documenta Ophthalmologica Volume: 131 Issue: 2 Pages: 115-124
  • DOI: 10.1007/s10633-015-9506-x
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 遭遇することの多い視神経疾患 (2015)
  • Author(s): 中村 誠
  • Journal Title: 日本医師会雑誌 Volume: 144 Pages: 1827-1830
• [Journal Article] Sera from patients with seropositive neuromyelitis optica spectral disorders caused the degeneration of rodent optic nerve (2014)
  • Author(s): Matsumoto Y, Kanamori A, Nakamura M, Takahashi T, Nakashima I, Negi A.
  • Journal Title: Experimental Eye Research Volume: 119 Pages: 61-69
  • DOI: 10.1016/j.exer.2013.12.010
  • Peer Reviewed
• [Journal Article] Rat chronic glaucoma model induced by intracameral injection of microbeads suspended in sodium sulfate-sodium hyaluronate (2014)
  • Author(s): Matsumoto, Y. Kanamori, A. Nakamura, M. Negi, A.
  • Journal Title: Jpn J Ophthalmol Volume: In press Issue: 3 Pages: 290-7
  • DOI: 10.1007/s10384-014-0311-y
  • NAID: 40020062481
  • Peer Reviewed
• [Journal Article] Effect of refractive errors on multifocal VEP responses and standard automated perimetry tests in a single population (2014)
  • Author(s): Nakamura M, Kato K, Kamata S, Ishikawa K, Nagai T
  • Journal Title: Documenta Ophthalmologica Volume: 128 Issue: 3 Pages: 179-189
  • DOI: 10.1007/s10633-014-9431-4
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The expression of syntaphilin is down-regulated in the optic nerve after axonal injury (2014)
  • Author(s): Miki A, Kanamori A, Nakamura M, Matsumoto Y, Mizokami J, Negi A
  • Journal Title: Exp Eye Res Volume: 129 Pages: 38-47
  • DOI: 10.1016/j.exer.2014.10.017
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 視神経・視路疾患と視野障害 (2016)
  • Author(s): 中村 誠
  • Organizer: 第70回日本臨床眼科学会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2016-11-05
  • Invited
• [Presentation] 難治性視神経症の診断・治療に対する最近の考え方 (2016)
  • Author(s): 中村 誠
  • Organizer: 第70回日本臨床眼科学会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2016-11-05
  • Invited
• [Presentation] 視神経炎における抗AQP4抗体の構造と機能に与える影響 (2016)
  • Author(s): 松本佳子、明石 梓、上田香織、坂本麻里、井上由結子、金森章泰、山田裕子、中村 誠
  • Organizer: 第120回日本眼科学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2016-04-07
• [Presentation] Structure and function: Why is the correlation not high? WGC Course Imaging for glaucoma diagnosis and monitoring: New idea from Asia. (2015)
  • Author(s): Makoto Nakamura
  • Organizer: 第6回World Glaucoma Congress
  • Place of Presentation: 香港
  • Year and Date: 2015-06-08
  • Int'l Joint Research / Invited
• [Presentation] 視神経炎の診断と治療．Up to date (2014)
  • Author(s): 中村 誠
  • Organizer: 第52回日本神経眼科学会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2014-12-12 – 2014-12-13
  • Invited
• [Presentation] 視神経脊髄炎関連視神経炎ラットに対するヒト免疫グロブリンの効果 (2014)
  • Author(s): 延吉章、金森章泰、松本佳子、中村 誠
  • Organizer: 第52回日本神経眼科学会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2014-12-12 – 2014-12-13
• [Presentation] 周辺視野を守る。 (2014)
  • Author(s): 中村 誠
  • Organizer: 第25回日本緑内障学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-09-20 – 2014-09-22
  • Invited
• [Presentation] アクアポリン9は乳酸輸送を介して網膜神経節細胞の生存を制御する (2014)
  • Author(s): 明石梓、三木明子、井上結香子、金森章泰、中西裕子、中村 誠
  • Organizer: 第25回日本緑内障学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-09-20 – 2014-09-22
• [Presentation] 視路疾患としての緑内障性視神経症 (2014)
  • Author(s): 中村 誠
  • Organizer: 第118回日本眼科学会総会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2014-04-06 – 2014-04-08
  • Invited
• [Book] オクリスタ No.13.視神経症のよりよい診療 (2014)
  • Author(s): 中村 誠
  • Total Pages: 83
  • Publisher: 全日本病院出版会
• [Remarks] 神戸大学医学部眼科学教室
  • URL: http://kobe-med-ganka.com/