| Project/Area Number |
11671754
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | KITASATO UNIVERSITY |
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Principal Investigator |
ICHIBE Yoshiaki (2002) Kitasato Univ. School of Medicine Assistant Professor, 医学部, 講師 (70265700)
若倉 雅登 (1999-2001) 北里大学, 医学部, 助教授 (50137931)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAKAMI Tadashi Kitasato Univ. School of Medicine Professor, 医学部, 教授 (60177649)
YAMAMOTO Noboru Kitasato Univ. School of Nursing Professor, 看護学部, 教授 (10050543)
市辺 義章 北里大学, 医学部, 講師 (70265700)
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| Project Period (FY) |
1999 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Muller cell / retinal neuron / neurotransmitter / glutamate / neuronal cell death / glutamate receptor / dopamine D1 receptor / dopamine D2 receptor / ドパミン / エルドーパ / 細胞内カルシウム濃度 / レボブノロール / 高倍率ビデオ増感顕微鏡 / 細胞内粒子運動 / 神経保護 / TUNEL法 / Comet法 / グルタミン酸アゴニスト / カルシウムチャネルブロッカー / L-dopa / ドパミン受容体 / 網膜 / NMDA / non-NMDA / 神経伝達物質受容体 / D_1受容体 / D_2受容体 / 細胞内カルシウムイオン濃度測光 / 細胞内粒子活動 |
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| Research Abstract |
Muller cells act as not only structurally supportive cells in the retina but also multifunctional cells. Neuro-transmitters are essential to exert normal neuronal function. As we previously indicated, a non-neuronal glial cell, Muller cell possesses glutamate receptors. The purpose of this study is to determine functional roles of neurotransmitter receptors on Muller cells. Excessive glutamate brings about neuronal cell death in the retina. On cultured retinal neurons and Muller cells, we examined neuronal cell death and its protection due to administration of excitotoxic glutamate agonists using TUNEL and Comet methods to detect cell death. After administration of N-methyl-D-aspartate (NMDA) at 2 mM or L-a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) at 5 mM increased significantly rate of cell death when compared to controls without agonist administration. The rate of neuronal and Muller cell death was pararell suggesting the same survival fatality of two kind of the cel
… More
ls. On the other hand, dopamine is a neurotransmitter suggested to have neuroprotective roles. Intracellular calcium concentrations were measured before and after administration of DA D1 receptor agonist (R(+)-SKF-82957) under several conditions using cell labeling of a calcium ion indicator, Fura-2 AM. Muller cells responded to D1 agonist with dose-dependent manner at concentrations among 10^<-6> and 10^<-3> M. From data obtained from video-enhanced microscopic recordings, which can be used to observe real-time intracellular movement of particles, the movement after administration of a D1 receptor agonist was diminished while after that after D2 agonist administration, facilitated, indicating contrast function of the two receptors. Glutamate agonist-induced cell death was significantly suppressed by prior treatment at a dopamine precursor, L-dopa at concentrations less than 10^<-6> M. Similar induction and suppression of cell death was also shown in cultured Muller cells. Based on our experiments, the neuroprotection of L-dopa appeared to occur through the D1 or D2 receptors. Muller cells may participate in the neuroprotective mechanisms. Less
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