| Project/Area Number |
11671723
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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 | Department of Ophthalmology, University of Tokyo Branch hospital, The University of Tokyo |
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Principal Investigator |
KATO Satoshi (2000) University of Tokyo Branch hospital, Dept of Ophthalmol., Lecturor, 医学部・附属病院・分院, 講師 (20214372)
加藤 聡 (1999) 東京大学, 医学部・附属病院・分院, 講師 (20277114)
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| Co-Investigator(Kenkyū-buntansha) |
NUMAGA Jiro Tokyo Metropolitan Geriatric Hospital, Sect of Ophthalmol., chief director, 眼科, 部長 (30189352)
FUJINO Yujiro Tokyo Kousei-Nenkin Hospital, Dept, of Ophthalmol., chief director, 眼科, 部長 (30143465)
KAWASHIMA Hidetoshi Univ.of Tokyo Branch hospital, Dept of Ophthalmol., Associate Prof., 医学部・附属病院・分院, 助教授 (30169718)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | retinitis / herpes simplex virus / herpetic retinitis / chemokine / MIP-2 / IP-10 / neutrophil / Th1 cell / Th1サイトカイン |
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| Research Abstract |
From the results of last year's research, it was clarified that not only cytokines such as 1FN-γ and TNF-α, but also chemokines sych as MIP-2, MCP-1, MIP-1α, RANTES, MIG, and IP-10 were expressed in eyes of the murine herpetic retinitis. Because chemokines have been believed to have important roles on recruiting leukocytes into inflammatory lesions, we examined the roles of chemokines in murine herpetic retinitis model. We prepared two neutralizing antibodies(Abs)against two distinct chemokines. The first one was against MIP-2 that might play roles on recruiting neutrophils in the early stage of the herpetic retinitis. The second one is against IP-10 that might affect the recruitment of Th1 cells. These Abs were administrated intravenously to the mice with herpetic retinitis.
The incidence of herpetic retinitis was reduced by anti-MIP-2 Ab administration. Infiltration of neutrophils in the left eyes was also reduced. On the contrary, the amount of the virus in the eyes was not significantly affected by the anti-MIP-2 Ab administration. Since the infiltration of neutrophils into the eyes at the early stages of herpetic retinitis was reduced by anti-MIP-2 Ab administration, the incidence of the retinitis could well be reduced consequentially.
In the next experiment, anti-IP-10 Ab was administered intravenously. The anti-IP-10 Ab controlled T cell infiltration into the eyes with the herpetic retinitis model. It also increased the amount of the virus in both eyes. In addition, herpetic retinitis developed earlier in the uninjected eyes. Incidence of the retinitis was also increased by anti-IP-10 Ab administration.
From these results, it was speculated that MIP-2 contributed to the excerbation of the herpetic retinitis by recruiting neutrophils into the eyes in the early stage of the inflammation, while IP-10 promoted the infiltration of activated T cells into the eyes, thus playing an important role in the virus removal in murine herpetic retinitis model.
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