The neuroprotective effects of diazoxide for the glaucoma model by NMDA and ischemia

• Project/Area Number: 18791307
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Ophthalmology
• Research Institution: Osaka Medical College
• Principal Investigator: OKUNO Takashi Osaka Medical College, 医学部, 非常勤講師 (20411366)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,760,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2007: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
• Keywords: 神経保護 / 緑内障 / 網膜神経節細胞 / 視覚誘発電位 / 網膜電図 / 視神経萎縮 / ウサギ / サル / 神経節細胞 / OGD誘発細胞死 / fluorescence activated cell sorting / mitchondria KATP channel / 5-hydroxydecanoic acid / in vivo

Research Abstract

まず、in vitro研究により、ジアゾキサイド(diazoxide)はラット網膜神経節細胞由来細胞株に対し細胞死の抑制効果があり、この効果はミトコンドリア内膜に存在する ATP 感受性リウムチャンネルを介していることが確認できた。
また、経時的に測定した視覚誘発電位や眼組織標本などを用いたin vitro研究においても、NMDAによる緑内障モデルの神経障害の回復を促進させ、神経保護作用を持つことがウサギおよびサルの両者において示された。

Research Products

• [Journal Article] Shift of temporal responsivity curve of pattern reversal visually evoked potentials to lower frequencies in patients after recovery from optic neuritis (2009)
  • Author(s): Okuno T, Oku H, Sugasawa J, Utsumi T, Iked T.
  • Journal Title: Acta Ophthalmol (in press)
  • Peer Reviewed
• [Journal Article] Peripheral cone dystrophy in an elderly man (2009)
  • Author(s): Okuno T, Oku H, Kurimoto T, Oono S, Ikeda T.
  • Journal Title: Clin Experiment Ophthalmol 36 Pages: 897-9
  • Peer Reviewed
• [Journal Article] Reduced retinal function in amyloid precursor protein-over-expressing transgenic mice via attenuating glutamate-N-methyl-d-aspartate receptor signaling (2008)
  • Author(s): Shimazawa M, Inokuchi Y, Okuno T, Nakajima Y, Sakaguchi G, Kato A, Oku H, Sugiyama T, Kudo T, Ikeda T, Takeda M, Hara H.
  • Journal Title: J Neurochem 107 Pages: 279-90
  • Peer Reviewed
• [Journal Article] Endothelin-1 (ET-1) is increased in rat retina after crushing optic nerve (2008)
  • Author(s): Oku H, Fukuhara M, Kurimoto T, Okuno T, Sugiyama T, Ikeda T.
  • Journal Title: Curr Eye Res 33 Pages: 611-20
  • Peer Reviewed
• [Journal Article] Electroretinographic study of spontaneously diabetic Torii rats (2008)
  • Author(s): Okuno T, Oku H, Sugiyama T, Ikeda T.
  • Journal Title: Doc Ophthalmol 117 Pages: 191-6
  • Peer Reviewed
• [Journal Article] Endothelin-1 (ET-1) causes death of retinal neurons through activation of nitric oxide synthase (NOS) and production of superoxide anion (2008)
  • Author(s): Oku H, Fukuhara M, Komori A, Okuno T, Sugiyama T, Ikeda T.
  • Journal Title: Exp Eye Res 86 Pages: 118-30
  • Peer Reviewed
• [Journal Article] Electroretinographic study of spontaneously diabetic Torii rats (2008)
  • Author(s): Takashi Okuno
  • Journal Title: Doc Ophthalmol 117 Pages: 191-196
  • Peer Reviewed
• [Journal Article] Endothelin-1 (ET-1) is increased in rat retina after crushing optic nerve (2008)
  • Author(s): Hidehiro Oku
  • Journal Title: Curr Eye Res 33
  • Peer Reviewed
• [Journal Article] Reduced retinal function in amyloid precursor protein-over-expressing transgenic mice via attenuating glutamate-N-methyl-d-aspartate receptor signaling (2008)
  • Author(s): Masamitsu Simazawa
  • Journal Title: J Neurochem 107 Pages: 279-290
  • Peer Reviewed
• [Journal Article] Endothelin-l (ET-1) causes death of retinal neurons through activation of nitric oxide synthase (NOS) and production of superoxide anion (2008)
  • Author(s): Hidehiro Oku
  • Journal Title: Exp Eye Res 86 Pages: 118-130
  • Peer Reviewed
• [Journal Article] Angiotensin II receptor blocker inhibits abnormal accumulation of advanced glycation end products and retinal damage in a rat model of type 2 diabetes (2007)
  • Author(s): Sugiyama T, Okuno T, Fukuhara M, Oku H, Ikeda T, Obayashi H, Ohta M, Fukui M, Hasegawa G, Nakamura N.
  • Journal Title: Exp Eye Res 85 Pages: 406-12
  • Peer Reviewed
• [Journal Article] High infusion pressure in conjunction with vitreous surgery alters the morphology and function of the retina of rabbits (2007)
  • Author(s): Minami M, Oku H, Okuno T, Fukuhara M, Ikeda T.
  • Journal Title: Acta Ophthalmol Scand 85 Pages: 633-9
  • Peer Reviewed
• [Journal Article] Angiotensin II receptor blocker inhibits abnormal accumulation of advanced glycation end products and retinal damage in a rat model of type2 diabetes (2007)
  • Author(s): Tetsuya Sugiyama
  • Journal Title: Exp Eye Res. 85 Pages: 406-412
  • Peer Reviewed
• [Journal Article] Abnormalities of visual-evoked potentials and pupillary light reflexes in a family with autosomal dominant occult macular dystrophy. (2007)
  • Author(s): Takashi Okuno
  • Journal Title: Clin Experiment Ophthalmol 35 Pages: 781-783
  • Peer Reviewed
• [Journal Article] Glutamate level in optic nerve head is increased by artificial elevation of intraocular pressure in rabbits (2006)
  • Author(s): Okuno T, Oku H, Sugiyama T, Ikeda T.
  • Journal Title: Exp Eye Res 82 Pages: 465-70
  • NAID: 10018257119
  • Peer Reviewed
• [Journal Article] Abnormalities of visual-evoked potentials and pupillary light reflexes in a family with autosomal dominant occult macular dystrophy (2006)
  • Author(s): Okuno T, Oku H, Kondo M, Miyake Y, Sugasawa J, Utsumi T, Ikeda T.
  • Journal Title: Clin ExperimentOphthalmol 35 Pages: 781-3
  • Peer Reviewed
• [Journal Article] Ocular blood flow changes after dynamic exercise in humans (2006)
  • Author(s): Okuno T, Sugiyama T, Kohyama M, Kojima S, Oku H, Ikeda T.
  • Journal Title: Eye 20 Pages: 796-800
  • Peer Reviewed
• [Journal Article] Glutamate level in optic nerve head is increased by artificial elevation of intraocular pressure in rabbits. (2006)
  • Author(s): Takashi Okuno
  • Journal Title: Exp Eye Res. 82(3) Pages: 465-470
  • NAID: 10018257119
• [Journal Article] Ocular blood flow changes after dynamic exercise in humans (2006)
  • Author(s): Takashi Okuno
  • Journal Title: Eye 20(7) Pages: 796-800
• [Journal Article] High infusion pressure in conjunction with vitreous surgery alters the morphology and function of the retina of rabbits
  • Author(s): Masahiro Minami
  • Journal Title: Acta Ophthalmol Scand. (in press)
• [Presentation] 低酸素状態における一酸化窒素の神経毒性 (2009)
  • Author(s): 奥英弘、福原雅之、奥野高司、勝村浩三、松尾純子、小嶌祥太、杉山哲也、池田恒彦
  • Organizer: 第112回日本眼科学会
  • Place of Presentation: 横浜
• [Presentation] 視神経乳頭循環自動調節能に対するグリア細胞の関与 (2009)
  • Author(s): 柴田真帆,杉山哲也,奥英弘,奥野高司,小林正人,平尾真美,池田恒彦
  • Organizer: 第112回日本眼科学会
  • Place of Presentation: 横浜
• [Presentation] 最終糖化産物(AGE)による網膜周皮細胞死に対するスタチンの抑制効果 (2009)
  • Author(s): 松尾純子、奥英弘、勝村ちひろ、杉山哲也、神原裕子、小林崇俊、福原雅之、奥野高司、池田恒彦
  • Organizer: 第112回日本眼科学会
  • Place of Presentation: 横浜
• [Presentation] 網膜神経節細胞株(RGC-5)に対するスタチンの神経保護作用の検討 (2008)
  • Author(s): 奥英弘,勝村浩三,松尾純子,奥野高司,小林崇俊,小嶌祥太,福原雅之,杉山哲也,池田恒彦
  • Organizer: 第112回日本眼科学会
  • Place of Presentation: 横浜
• [Presentation] アミロイドβ蛋白質の網膜機能および細胞死に対する影響 (2008)
  • Author(s): 嶋澤雅光,井口勇太,奥野高司,坂口岳,加藤晃,奥英弘,杉山哲也,工藤喬,池田恒彦,武田雅俊,原英彰
  • Organizer: 第112回日本眼科学会
  • Place of Presentation: 横浜
• [Presentation] SDTラットの網膜電図に対するアンジオテンシンII受容体拮抗薬の効果 (2007)
  • Author(s): 奥野高司,奥英弘,杉山哲也,小森麻子,池田恒彦
  • Organizer: 第55回日本臨床視覚電気生理学会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-11-03
• [Presentation] Involvement of Amyloid-β in Retinal Function (2007)
  • Author(s): Shimazawa M, Inokuchi Y, Okuno T, Sakaguchi G, Kato A, Sugiyama T, Kudo T, Ikeda T, Takeda M, Hara H.
  • Organizer: 79th Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Florida, USA.
• [Presentation] Endothelin-1 (ET-1) Causes Death of Retinal Neurons Through Activation of Nitric Oxide Synthase (NOS) and Production of Superoxide Anion (2007)
  • Author(s): Oku H, Fukuhara M, Komori A, Okuno T, Sugiyama T, Ikeda T.
  • Organizer: 79th Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Florida, USA.
• [Presentation] ラット視神経挫滅モデルにおける網膜内エンドセリン-1の変化 (2007)
  • Author(s): 奥野高司,奥英弘,福原雅之,杉山哲也,池田恒彦
  • Organizer: 第111回日本眼科学会
  • Place of Presentation: 大阪
• [Presentation] NMDA 誘発網膜内層障害に対するミトコンドリア内膜カリウムチャネル開口薬の効果 (2007)
  • Author(s): 奥野高司,奥英弘,杉山哲也,小森麻子,池田恒彦
  • Organizer: 第110回日本眼科学会
  • Place of Presentation: 大阪
• [Presentation] SDTラット眼内・蛋白糖化最終産物に対するアンジオテンシンII受容体拮薬の作用 (2007)
  • Author(s): 杉山哲也,奥野高司,福原雅之,小森麻子,奥英弘,池田恒彦,太田光煕,尾林博
  • Organizer: 第110回日本眼科学会
  • Place of Presentation: 大阪
• [Presentation] Temporal frequency changes in the pattern reversal visual evoked potential (PVEP) amplitude in optic neuritis (2006)
  • Author(s): Okuno T, Oku H, Sugasawa J, Utsumi T, Ikeda T.
  • Organizer: 16th International Neuron-Ophthalmology Society (INOS) Congress
  • Place of Presentation: Tokyo, Japan