2003 Fiscal Year Final Research Report Summary
The Role of Angiotensin II Receptor Subtype in Ocular Injury
| Project/Area Number |
14370559
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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 | Ehime University |
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Principal Investigator |
OHASHI Yuichi Ehime University, School of Medicine, Professor, 医学部, 教授 (00116005)
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| Co-Investigator(Kenkyū-buntansha) |
HORIUCHI Masatsugu Ehime University, School of Medicine, Professor, 医学部, 教授 (40150338)
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| Project Period (FY) |
2002 – 2003
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| Keywords | angiotensin / wound healing / receptor / conjunctiva / cornea / collagen / TIMP / MMP |
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| Research Abstract |
Angiotensin II (Ang II) plays an important role in the regulation of cardiovascular structure and hemodynamics. Two major Ang II receptor subtypes, named type 1 (AT_1) and type 2 (AT_2) receptors, have been previously reported. Recent studies suggest that Ang II regulates wound healing process through these receptors. However, the detailed mechanism is not clarified We investigated the role of AT_1 and AT_2 receptor subtypes in ocular injury using wound healing model.
1.Subconjunctival wound healing : Wound healing model was developed by subconjuncival blunt dissection in male wild type (WT ; C57BL/6J), AT_<1a> null (AT_<1a>KO) and AT_2 null (AT_2KO) mice. Subconjunctival injury induced collagen deposition. Subconjunctival collagen deposition detected by histological analysis at 14 days after injury was higher in AT_2KO mice than in WT mice, but it was lower than in AT_<1a>KO mice than in WT mice. The level of mRNA for type 1 collagen at 7 days was increased in subconjunctival tissue including conjunctiva after injury. This increase was significantly higher in AT_2KO mice, but it was lower than in AT_<1a>KO mice than in WT mice. To examine the mechanism of action of AT1 and AT2 receptors on collagen synthesis regulation, we assayed the expression of TIMP-1. The level of mRNA was also increased at 12 hours after injury after subconjuntival damage. However, the increase in TIMP-1 expression was significantly higher in AT_<1a>KO mice, but lower than in AT_2KO mice than in WT mice.
2. Corneal epithelial wound healing : Corneal epithelial wound healing model was made by eximer lazar in male WT and AT_<1a>KO mice. AT_<1a>KO mice delayed corneal epithelial wound healing compared to WT mice. The BrdU index in epithelial cells was lower in the AT_<1a>KO mice than in the WT mice.
These results suggest that AT_1 and AT2 receptor subtypes play an important role in the regulation of ocular injury.
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