Project/Area Number |
12671694
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Ophthalmology
|
Research Institution | Tohoku University |
Principal Investigator |
ABE Toshiaki Ophthalmology, Tohoku Univ., Associate professor, 大学院・医学系研究科, 助教授 (90191858)
|
Co-Investigator(Kenkyū-buntansha) |
TOMITA Hiroshi Ophthalmology, Tohoku Univ., Research Associate, 大学院・医学系研究科, 助手 (40302088)
|
Project Period (FY) |
2000 – 2001
|
Project Status |
Completed (Fiscal Year 2001)
|
Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
|
Keywords | age-related macular degeneration / retinal pigment epithelium / cytokine / hypoxia / serum / VEGF / bFGF / TGFB / bFTGFβ / TGFβ |
Research Abstract |
Patients with age-related macular degeneration (AMD) generate variable degree of submacular hemorrhage, exudates, and retinal detachment and so on due to the submacular choroidal neovascularization (CNV). There have been no reports to treat the disease safely and steady and patients forced to be limited quality of life. One of the reasons is the unknown mechanism of the generation of the neovascular membranes. We examined the mRNA expression in the CNV from patients with AMD and compared them to those of other proliferative membranes from patients with proliferative vitreoretinopathy (PVR) and diabetic retinopathy (PDR). Statistically significant, expression of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and transforming growth factor (TGF) beta was observed in the membrane of CNV when compared to those of PVR and PDR. bFGF expression increased with the enlargement of CNV, conversely VEGF and TGF beta expressed remarkably when the membranes were small size. We found bFGF and VEGF co-stimulated the enlargement of the CNV, conversely TGF beta inhibits the enlargement of the CNV using in vitro model of angiogenesis. We also found that hypoxia increase the expression of VEGF in the retinal pigment epithelium (RPE). The fact may be coincident with the previous report that hypo-perfusion may affect the generation of the CNV at the submacular lesions. Further, we examined the barrier function of the RPE using microporous filter support in the medium with several cytokines including VEGF and bFGF. The results revealed that VEGF might affect the barrier function of the RPE, but interleukin-1beta showed prominent effect for disrupting the function.
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