2001 Fiscal Year Final Research Report Summary
Establishment of experimental local gene therapy model for uveitis
| Project/Area Number |
11671743
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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 | KYUSHU UNIVERSITY |
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Principal Investigator |
KAWANO Yoh-ichi Kyushu university, Department of Ophthalmology, Lecturer, 医学部・附属病院, 講師 (90211185)
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| Project Period (FY) |
1999 – 2001
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| Keywords | Uveitis / gene therapy / adeno virus / VEGF / CD8 / CCR2 |
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| Research Abstract |
Uveitis has become increasingly recognized as a major cause of blindness, especially in the working age population. The main cause of the irreversible damage of the eye depends on the relapse of the inflammation which is hard to suppress with the immunosuppressive agents in some entities of uveitis. The aim of the study of this period was to establish experimental model of the gene therapy for uveitis, targeted for the functional molecules that is involved for the cellular immune reaction.
We initially tested the efficacy of the LacZ gene transfer by adenovirus vecter in rat. Injection of the vector into anterior chamber and the vitreous cavity caused gene expression in angle and retinal ganglion cells but not in ciliary body and choroid. Injection into the eye with experimental uveitis decreased efficacy of the transfer. Subretinal injection of the vector caused gene expression in RPE and infiltrated leucocytes. These results showed the necessity of the novel methods for the gene transfer into uveal tissue.
To find out the effect of the genetical modulation of the functional molecules involved in the inflammation on uveitis, we tested the susceptibility for EAU induction in the CD8 KO mice and CCR2 KO mice. EAU were accerelated in CD8 KO mice, and the type of infiltrating innflammatory cells were changed in CCR2 KO mice. These results show the possibilty of the immunomodulation by the gene therapy targeted for these molecules.
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