| Co-Investigator(Kenkyū-buntansha) |
YUSUF Durlu K Same as above Faculty, 医学部・付属病院, 助手 (90250787)
YAMADA Takahiko Same as above Assistant Prof., 医学部・付属病院, 講師 (40191316)
ISHIGURO Seiichi Same as above Assistant Prof., 医学部, 講師 (20111271)
荒川 明 東北大学, 医学部・附属病院, 医員
加藤 圭一 東北大学, 医学部・附属病院, 助手 (50260435)
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| Budget Amount *help |
¥25,400,000 (Direct Cost: ¥25,400,000)
Fiscal Year 1996: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1995: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1994: ¥14,400,000 (Direct Cost: ¥14,400,000)
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| Research Abstract |
Age-related macular degeneration is one of the most serious diseases in the elderly people. Even if submacular and choroidal neovascular membrane could be surgically excised, severe damage or evacuation of retinal pigment epithelium are innevitable in the operated area. Pigmentary dystrophy is also a devastating hereditary eye disease with severe visual disturbance. Up to now, we have no effective treatments for both of them. We have conducted basic experiments of retinal pigment epithelium (RPE) culture, their transplantation to subretinal space of animals, especially, the royal college of surgeon's (RCS) rat, a model of hereditary retinal degeneration and observed their rescue effects for photoreceptor cell death.
1) With the retinal dystrophic RCS rat, we transplanted RPE from Long Evans rat, human, and bovine and could observe the retardation of the photoreceptor cell death.
2) RPE cells from eye bank eye or fetus eye were easily obtained and cultured. They were transplanted as fresh
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or cultured with primary or multiple passage. We also tried cryopreservation of these cells up to 3 months. Their characteristics were well preserved at least in the viewpoints of several gene expression. In the future, if we could keep these RPE cells in deep-freezed condition, we could use them clinically in appropriate time and number of cells for patients just as "RPE bank".
3) In experimental animals, they did not show any immunological reaction. But transplantation of human RPE cells with collagen sheet into the anterior chamber in rabbit showed difinite reaction like suppression of electroretinogram and macrophage infiltration in the subretinal space, not only in the operated but contralateral non-operated eye. These results suggest we must be cautious in clinical application of heterogenous RPE transplantation. It was an interesting observation that the expression of MHC class II cells were observed in the course of photoreceptor cell degeneration in the RCS rat but supressed if they were rescued by the transplantation of human cultured RPE in these animals.
4) If we cpnsider clinical application of this technique, it is natural the autograft is much better than the xeno-or allograft. We tried to use the iris pigment epithelium (IPE) for transplantation because they were neural origin, pigmented cells and easily and enough amount of them were obtained by peripheral iridectomy. IPE of rat were cultured the vector (pCNX2) with cDNA of rat bFGF were transfected and transplanted into the subretinal space of RCS rat. These transfected cells expressed strong mRNA of bFGF.The photoreceptors were well preserved and no immunological reaction. If we could use IPE,either wild or modified with molecular technique, they were applicable for patients, much safer and easier. Less
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