2002 Fiscal Year Final Research Report Summary
Research on the non-nerve communicative function of the neurotransmitter in the retina
| 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 Kitasato Univ. School of Medicine Assistant Professor, 医学部, 講師 (70265700)
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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)
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| Project Period (FY) |
1999 – 2002
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| Keywords | Muller cell / retinal neuron / neurotransmitter / glutamate / neuronal cell death / glutamate receptor / dopamine D1 receptor / dopamine D2 receptor |
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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
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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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