| Project/Area Number |
12557226
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
HOSOYA Ken-ichi Toyama Medical and Pharmaceutical University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (70301033)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAZU Kouichi Santen Pharmaceutical Co, Ophthalmic Research Division, General Manager, 眼科研究所・動態研究グループ, マネージャー(研究職)
OBINATA Masuo Tohoku University, Institute of Development, Aging and Cancer, Associate Professor, 加齢医学研究所, 教授 (10099971)
KATAYAMA Kazunori Toyama Medical and Pharmaceutical University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (70126514)
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| Project Period (FY) |
2000 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2001: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Keywords | blood-retinal barrier / conditionally immortalized cell line / co-culture / system xc- / LAT1 / Muller cell / GLUT1 / vitamin C / TR-MUL細胞 / 内側血液網膜関門 / 酸化的ストレス / TR-iBRB細胞 / アミノ酸輸送 / TAUT / 浸透圧 / Muller細胞株 / GLAST / 培養細胞株 / 眼 / ペリサイト株 / α-smooth muscle actin / intercellular adhesion molecule-1 |
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| Research Abstract |
Conditionally immortalized rat retinal pericyte cell line(TR-rPCT) and Mailer cell line(TR-MUL) were established from transgenic rats harboring the temperature-sensitive SV 40 large T-antigen gene(tsA58 Tg rat). TR-rPCT and TR-MUL cells have pericyte and Muller cell markers and functions in vivo. These cell lines can be applied in co-culture with previously established conditionally immortalized rat retinal capillary endothelial cell line TR-iBRB). The co-culture studies suggest that soluble factors from TR-rPCT cells suppress the activation of PKC-p44/42 MAPK signaling and the expression of cyclin D1,cdk4,and cdk6,inhibit endothelial cell growth. Using TR-iBRB cells and TR-MUL cells, L-cystine transporter, system xc-was expressed and functioned at the inner blood-retinal barrier and plays a role in supplying L-cystine as a precursor of an antioxidant to the retina. TR-iBRB cells and TR-MUL cells expressed xCT and 4F2hc mRNA and protein and xCT was induced under oxidative stress conditions following diethyl maleate treatment. Vitamin C acts as an antioxidant and/or free radical scavenger to detoxify free radicals in the retina. GLUT1 is expressed in TR-iBRB cells and TR-MUL cells and transports dehydroascorbic acid, oxidized form of vitamin C. These results suggest that GLUT1 at the inner blood-retinal barrier plays a role in supplying vitamin C to the retina. TR-iBRB cells express LAT1 and have transport functions of neutral amino aqids, suggesting that LAT1 is expressed at the inner blood-retinal barrier and plays a role in supplying neutral amino acids to the retina. These findings suggest newly developed conditionally immortalized cell lines are useful in vitro models to study the inner blood-retinal barrier transport functions.
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