Involvement of aquaporin 4 in macular edema and its possible treatment

• Project/Area Number: 15K10909
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Osaka Medical College
• Principal Investigator: Kida Teruyo 大阪医科大学, 医学部, 講師 (90610105)
• Co-Investigator(Kenkyū-buntansha): 奥 英弘 大阪医科大学, 医学部, 准教授 (90177163)
• Research Collaborator: HORIE Taeko 大阪医科大学, 医学部, 研究助手
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: アクアポリン4 / 糖尿病 / 黄斑浮腫 / ミュラー細胞 / VEGF / TGN-020 / 一酸化窒素 / LSFG-Micro / アクアポリン４ / 網膜血管細胞

Outline of Final Research Achievements

Aquaporin 4 (AQP4), a water channel protein, is known to be expressed in retinal Muller cells. The purpose of this study was to determine the effects of VEGF and AQP4 channels on the volumetric changes in Muller cells.
presence or absence of VEGF and TGN-020, a selective AQP4 inhibitor.
In the diabetic rat retina, VEGF immunoreactivity was concentrated in the internal retinal layers, and AQP4 immunoreactivity was higher than controls. The expressions of AQP4 were colocalized with GFAP. Protein levels of VEGF in the hyperglycemic rat retina were significantly higher than controls. FACS analyses showed that exposure to VEGF enlarged Muller cells, while exposure to TGN-020 suppressed the enlargement. Intracellular levels of NO were increased after exposure to VEGF, which was suppressed following the addition of TGN-020. The observed Muller cell swelling is mediated by VEGF and AQP4.

Research Products

• [Journal Article] Development of macular retinoschisis long after the onset of retinal arterial occlusion (RAO): a retrospective study (2018)
  • Author(s): Ishizaki N, Kida T, Fukumoto M, Sato T, Oku H, Ikeda T.
  • Journal Title: BMC Ophthalmol Volume: 18 Issue: 1 Pages: 59-59
  • DOI: 10.1186/s12886-018-0730-5
  • Peer Reviewed
• [Journal Article] Implication of VEGF and AQP4 mediating Muller cell swelling to diabetic retinal edema. (2017)
  • Author(s): Kida T, Oku H, Horie T, Fukumoto M, Okuda Y, Morishita S, Ikeda T.
  • Journal Title: Graefes Arch Clin Exp Ophthalmol Volume: 印刷中 Issue: 6 Pages: 1149-1157
  • DOI: 10.1007/s00417-017-3631-z
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Long-term evaluation of spontaneous release of epiretinal membrane and its possible pathogenesis (2017)
  • Author(s): Kida T, Morishita S, Fukumoto M, Sato T, Oku H, Ikeda T
  • Journal Title: Clin Ophthalmol Volume: 11 Pages: 1607-1610
  • DOI: 10.2147/opth.s146692
  • Peer Reviewed / Open Access
• [Journal Article] P7C3 Suppresses Neuroinflammation and Protects Retinal Ganglion Cells of Rats from Optic Nerve Crush. (2017)
  • Author(s): Oku H, Morishita S, Horie T, Kida T, Mimura M, Kojima S, Ikeda T.
  • Journal Title: Investigative Ophthalmology & Visual Science Volume: 58 Issue: 11 Pages: 4877-4888
  • DOI: 10.1167/iovs.17-22179
  • Peer Reviewed / Open Access
• [Journal Article] Protective effect of P7C3 on retinal ganglion cells from optic nerve injury. (2017)
  • Author(s): Oku H, Morishita S, Horie T, Nishikawa Y, Kida T, Mimura M, Kojima S, Ikeda T.
  • Journal Title: Jpn J Ophthalmol Volume: 61 Issue: 2 Pages: 195-203
  • DOI: 10.1007/s10384-016-0493-6
  • NAID: 210000165803
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Negative impact of AQP-4 channel inhibition on survival of retinal ganglion cells and glutamate metabolism after crushing optic nerve. (2016)
  • Author(s): Nishikawa Y, Oku H, Morishita S, Horie T, Kida T, Mimura M, Fukumoto M, Kojima S, Ikeda T.
  • Journal Title: Exp Eye Res Volume: 146 Pages: 118-127
  • DOI: 10.1016/j.exer.2015.12.012
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] NADPH oxidase-mediated ROS production determines insulin’s action on the retinal microvasculature. (2015)
  • Author(s): Kida T, Oku H, Horie T, Matsuo J, Kobayashi T, Fukumoto M, Ikeda T
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 56 Issue: 11 Pages: 6754-6761
  • DOI: 10.1167/iovs.15-17534
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Nitric Oxide Increases the Expression of Aquaporin-4 Protein in Rat Optic Nerve Astrocytes through the Cyclic Guanosine Monophosphate/Protein Kinase G Pathway. (2015)
  • Author(s): Oku H, Morishita S, Horie T, Kida T, Mimura M, Fukumoto M, Kojima S, Ikeda T.
  • Journal Title: Ophthalmic Res Volume: 54 Issue: 4 Pages: 212-221
  • DOI: 10.1159/000440846
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 高血糖状態におけるVEGFとアクアポリン4を介した網膜ミュラー細胞の変化 (2017)
  • Author(s): 喜田照代、奥 英弘、堀江妙子、福本雅格、奥田義隆、森下清太、池田恒彦
  • Organizer: 第121回日本眼科学会総会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2017-04-06
• [Presentation] 高血糖状態におけるVEGFとアクアポリン4を介した網膜ミュラー細胞の変化 (2017)
  • Author(s): 喜田照代、奥 英弘、堀江妙子、福本雅格、奥田義隆、森下清太、池田恒彦
  • Organizer: 日本眼科学会総会
• [Presentation] Possible involvement of aquaporin 4 and nitric oxide in the high glucose-induced swelling of Muller cells in rat retina. (2016)
  • Author(s): Teruyo Kida, Hidehiro Oku, Masanori Fukumoto, Yoshitaka Okuda, Seita Morishita, Taeko Horie, Hiroyuki Suzuki, Takatoshi Kobayashi, and Tsunehiko Ikeda
  • Organizer: ARVO(Association for Research in Vision and Ophthalmology )
  • Place of Presentation: シアトル(アメリカ合衆国)
  • Year and Date: 2016-05-01
  • Int'l Joint Research
• [Presentation] シンポジウム (2016)
  • Author(s): 喜田照代
  • Organizer: 第120回日本眼科学会総会
  • Place of Presentation: 仙台国際センター(宮城県・仙台)
  • Year and Date: 2016-04-07
  • Invited