| Project/Area Number |
18591934
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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 | Juntendo University |
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Principal Investigator |
EBIHARA Nobuyuki Juntendo University, School of Medicine, senior associate professor (20255699)
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| Co-Investigator(Kenkyū-buntansha) |
FUNAKI Toshinari Juntendo University, School of Medicine, associate professor (80384121)
KAWANO Hiroyuki Juntendo University, School of Medicine, associate professor (70234094)
MURAKAMI Akira Juntendo University, School of Medicine, professor (90157743)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,930,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | vernal keratoconiunctivitis / chymase / TGF- β / occludin / SCF / corneal epithelial cell / fibroneitin / corneal myofibroblast / 形質転換 / 細胞外基質 / バリアー機能 / アポトーシス |
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| Research Abstract |
We determined the level of mast cell chymase activity in the tears of patients with vernal keratoconjunctivitis. High chymase activity was detected in the tear of VKC patients. The degree of these activity correlated significantly with VKC severity (r=0.9245, p<0.001).
Next, we investigated the in vitro effects of chymase on corneal epithelial cells. Chymase caused the proteolysis of occludin and fibronectin, resulting in a decrease of barrier function and inhibition of migration of corneal epithelial cells. In addition, chymase released and activated TGF-β_1 from extracellular matrix produced by corneal epithelial cell. Released TGF-β_1 transdifferentiated keratocytes to corneal myofibroblasts. Corneal myofibroblasts produced a large amount of stem cell factor. Stem cell factor is an important molecule, which has a crucial role in proliferation, maturation and chemotaxis for mast cell. We speculate the existence of a positive feed-back loop in which chymase differentiate keratocyte to myofibroblasts via TGF-β_1 , and myofibroblasts in turn stimulate mast cell via SCF.
The findings of our study that targeting chymase may lessen the severity of corneal complications in VKC. Specific inhibitors of chymase should become available in the future.
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