| Project/Area Number |
15390523
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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 | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | Hirosaki University |
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Principal Investigator |
OHGURO Hiroshi Hirosaki University, School of Medicine, Associate Professor, 医学部, 助教授 (30203748)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAZAWA Mitsuru Hirosaki University, School of Medicine, Professor, 医学部, 教授 (80180272)
OHGURO Ikuyo Hirosaki University, School of Medicine, Lecturer, 医学部, 講師 (90305235)
MAMIYA Kazuhisa Hirosaki University, University Hospital, Instructor, 医学部附属病院, 助手 (60344610)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 2005: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2004: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2003: ¥5,900,000 (Direct Cost: ¥5,900,000)
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| Keywords | retinal degeneration / rhodopsin / photoreceptor cell / calcium channel blocker / electroretinogram / retinoid / anthocyanin / retinitis pigmentosa / 網膜変性症 / モデル動物 / ロドプシンキナーゼ / 癌関連網膜症 / DNA microarray / 薬物治療 / Ca2+拮抗剤 / アポトーシス / 燐酸化 |
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| Research Abstract |
Retinitis pigmentosa (RP) is a disease of inherited retinal degeneration characterized by nyctalopia, ring-scotoma and bone-spicule pigmentation of the retina. So far, no effective therapy has been available for RP. As possible molecular etiology of RP, retina specific gene deficits are most likely involved but little has been identified in terms of intracellular mechanisms leading to retinal photoreceptor cell death at post translational levels.
In the present study, several animal models with different causes including 1)RCS rat with deficit of retinal pigment epithelium (RPE) function, 2)P23H,S334ter and photo-stress model with deficit of rhodopsin function, 3)rd mouse with deficit of phosphodiesterase (PDE) function and 4)cancer-associated retinopathy (CAR) model with deficit of recoverin-dependent photoreceptor adaptation function were studied their 1)retinal function by electroretinogram (ERG), 2)retinal morphology, 3)retinoid analysis, 4)rhodopsin regeneration, 5)rhodopsin phosph
… More
orylation and dephosphorylation and 6)cytosolic cGMP levels in order to elucidate common pathological mechanisms among these models. As a result, we found that misregulation of photoreceptor adaptation processes caused by imbalance of rhodopsin phosphorylation and dephosphorylation caused retinal dysfunction leading to photoreceptor cell death.
As possible candidate drugs normalizing these retinal dysfunction and stop further retinal degeneration, nilvadipine, a Ca channel blocker, retinoid derivatives and anthocyanine were choose and tested to their effect toward several animal models with retinal degeneration as above. Nilvadipine showed beneficial effects toward retinal degeneration in all models tested, but retinoid derivatives and anthocyanine showed these effects in only some models. Thus our present data allowed us to test nilvadipine to human RP patients. Prospective study using nilvadipine for 1.5 years revealed RP patients used nilvadipine administration showed significant lower progression in static perimetric analysis as compared to those without nilvadipine administration. In conclusion, nilvadipine is one of promising drug for preventing retinal degeneration RP patients. Less
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