Molecular analyses of glaucoma-associated mutations in OPTN gene and retinal blood flow
| Project/Area Number |
24791885
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Ophthalmology
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| Research Institution | 独立行政法人国立病院機構(東京医療センター臨床研究センター) |
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Principal Investigator |
MINEGISHI Yuriko 独立行政法人国立病院機構(東京医療センター臨床研究センター), 分子細胞生物学研究部, 研究員 (20621832)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 緑内障 / 家族性緑内障 / 遺伝子変異 / オプチニューリン / Optineurin / E50K / 正常眼圧緑内障 / 遺伝性疾患 / 神経変性疾患 / E50K変異 / 緑内障変異 / 分子細胞生物学 |
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| Research Abstract |
The optineurin (OPTN) E50K mutation was first identified in familial glaucoma. We have previously described an E50K mutation-carrying transgenic (E50K-tg) mouse that exhibited glaucomatous phenotypes. Further phenotypic analysis of these E50K-tg mice revealed the abnormal localization of E50K mutant protein deposits in retina, indicating a mutant protein aggregation/insolubility. Neurons derived from induced pluri potent stem cells (iPSCs) from E50K-glaucoma patients exhibited increased insolubilized OPTN. The E50K mutant strongly interacted with TBK1 and treatment with a TBK1 inhibitor abrogated the aberrant insolubility of E50K. Here, we delineated the underlying pathoetiology of E50K-glaucoma associating with mutant protein aggregation.
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Report
(3 results)
Research Products
(19 results)
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[Presentation] Distinct protein complex formation evokes insolubility of OPTN and mislocalization in iPSC-derived neural cells from E50K-POAG patients2013
Author(s)
Minegishi, Y., Iejima, D., Kobayashi, H., Chi., ZL., Kawase, K., Yamamoto, T., Seki, T., Yuasa, S., Fukuda, K., Iwata, T
Organizer
ARVO2013
Place of Presentation
Seattle, WA, USA
Year and Date
2013-05-05
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[Presentation] Distinct protein complex formation evokes insolubility of OPTN and mislocalization in iPSC-derived neural cells from E50K-POAG patients
Author(s)
Minegishi, Y., Iejima, D., Kobayashi, H., Chi1., ZL., Kawase, K., Yamamoto, T., Seki, T., Yuasa, S., Fukuda, K., Iwata, T
Organizer
ARVO2013 Annual Meeting
Place of Presentation
シアトル、アメリカ
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