Analysis of molecular mechanisms of viral growth and immune reaction in ocular herpetic infections
| Project/Area Number |
15390531
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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 | Tottori university |
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Principal Investigator |
INOUE Yoshitsugu Tottori University, Faculty of Medicine, Professor, 医学部, 教授 (10213183)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Dai Tottori University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (30346358)
下山 玲子 鳥取大学, 医学部附属病院, 助手 (50346342)
三原 悦子 鳥取大学, 医学部, 助手 (10335515)
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| Project Period (FY) |
2003 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥12,200,000 (Direct Cost: ¥12,200,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2003: ¥5,900,000 (Direct Cost: ¥5,900,000)
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| Keywords | herpes simplex virus / herpetic stromal keratitis / chemokine receptor / cornea / trigeminal ganglia / real-time PCR / Th1 cells / cytokine / 上皮型角膜ヘルペス / 角膜ヘルペス / ヘルペス性角膜内皮炎 / 角膜上皮細胞 / ケモカイン / T細胞 |
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| Research Abstract |
1. Pathpgenesis of herpetic stromal keratitis in CCR5- and CXCR3-deficient mice.
We have analyzed two chemokine receptors, CCR5 and CXCR3, which are expressed on CD4+ Th1 cells, in mice herpetic stromal keratitis (HSK) model. CCR5-deficient (CCR5KO), CXCR3-deficient (CXCR3KO), CCR5/CXCR3 double-deficient (DKO) and wild type (WT) mice were infected intracorneally with HSV-1 and examined clinically by biomicroscope. HSK clinical scores in DKO mice were significantly decreased compared with WT mice, which was reversed by the transfer of spleen cells of WT mice. Histologically, corneal infiltrating cells, including T cells (CD4+ and CD8+ cells) and neutrophils were significantly reduced in CCR5KO, CXCR3KO, and DKO mice. Transcript levels of immune-related cell surface marker in the eye were reduced in DKO mice. There were no significant differences of virus titers in eyes among any groups of mice. Collectively, the suppression of chemotaxis and activation of CD4+ Th1 cells by the lacking of
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CXCR3 and CCR5 caused the decrease of other infiltrating cells, resulting in the reduction of HSK without any increase of viral growth.
2. Clinical application of real-time polymerase chain reaction for diagnosis of herpetic diseases of anterior segment of the eye
To assess the value of quantification of herpes simplex virus (HSV)-DNA for the differential diagnosis of herpetic diseases of the anterior segment of the eye, 144 samples of 90 patients with ocular inflammatory diseases were examined for HSV-DNA by real-time PCR. In cases of typical herpetic epithelial keratitis, a high number of copies of HSV-DNA were detected (mean : 1.0×10^7 copies in epithelial scrapings and 3.5×10^5 copies in tear fluid). In stromal keratitis, the copies of HSV-DNA in the tear fluid (mean : 4.7×10^2 copies) was significantly lower than that in cases of epithelial keratitis. In the cases tested to exclude HSV, 17.0% showed low copy numbers of HSV-DNA indicating an unexpected involvement of HSV in these cases. Collectively, real-time PCR is an informative method to diagnose herpetic eye diseases and evaluate the possible involvement of HSV in other inflammatory ocular diseases. Less
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Report
(5 results)
Research Products
(27 results)
