Involvement of aquaporin in the formation of optic nerve edema and protective effects of blocking the AQP channels.

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462763
• 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: Oku Hidehiro 大阪医科大学, 医学部, 准教授 (90177163)
• Co-Investigator(Kenkyū-buntansha): Fukuhara Masayuki 大阪医科大学, 医学部, 非常勤講師 (00238510) ; Kobayashi Takatoshi 大阪医科大学, 医学部, 講師 (10567093) ; Okuno Takashi 大阪医科大学, 医学部, 非常勤講師 (20411366) ; Ikeda Tsunehiko 大阪医科大学, 医学部, 教授 (70222891) ; Ishizaki Eisuke 大阪医科大学, 医学部, 非常勤講師 (70530434) ; Takai Shinji 大阪医科大学, 医学部, 教授 (80288703) ; Kida Teruyo 大阪医科大学, 医学部, 講師 (90610105)
• Co-Investigator(Renkei-kenkyūsha): Hara Hideaki 岐阜大学, 薬学部, 教授 (20381717)
• Research Collaborator: Morishita Seita 大阪医科大学, 医学部, 大学院生 ; Kakurai Keigo 大阪医科大学, 医学部, 大学院生 ; Horie Taeko 大阪医科大学, 研究補助員
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: aquaporin / グルタミン酸 / 一酸化窒素 / 視神経挫滅 / アストロサイト

Outline of Final Research Achievements

Crushing the optic nerve of rats caued 1.8 fold increae of aquaporin 4 (AQP4) expression in the optic nerve. Exposure of optic nerve astrocytes to nitric oxide increased AQP4 expression and enlarged their volume.
Blocking the AQP4 channel by TGN-020 (5.0 mg/kg) caused more decrease of f retinal ganglion cells (RGCs). The ratio of BAX/Bcl-2 also supported the idea that blocking the AQP4 channel was neurodestructive. The glutamate level in the optic nerve was significantly increased after crushing the optic nerve, but TGN-020 depressed the expression of glutamate metabolism-related proteins. Exposure of cultured optic nerve astrocytes to glutamate increased the expression of AQP4 that was also depressed by TGN-020. In addition, glutamate uptake was inhibited by TGN-020. These results indicate that an inhibition of AQP4 enhances neuronal damages after crushing the optic nerve. Inhibition of AQP4 impairs glutamate metabolism which may account for these neurodestructive events.

Free Research Field

眼科