Study of the neovasucular membranes in patients with age-related macular degeneration

年龄相关性黄斑变性患者新生血管膜的研究

基本信息

批准号：
12671694
负责人：
ABE Toshiaki
金额：
$ 2.43万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671694/
关键词：
age-related macular degeneration retinal pigment epithelium cytokine hypoxia serum VEGF bFGF TGFB bFTGFβ TGFβ

项目摘要

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.

年龄相关性黄斑变性（AMD）患者由于黄斑下脉络膜新生血管（CNV）而产生不同程度的黄斑下出血、渗出、视网膜脱离等。目前尚无安全、稳定治疗该疾病的报道，患者的生活质量被迫受到限制。原因之一是新生血管膜的生成机制尚不清楚。我们检查了 AMD 患者 CNV 中的 mRNA 表达，并将其与增殖性玻璃体视网膜病变 (PVR) 和糖尿病视网膜病变 (PDR) 患者的其他增殖膜的 mRNA 表达进行了比较。与 PVR 和 PDR 相比，CNV 膜中碱性成纤维细胞生长因子 (bFGF)、血管内皮生长因子 (VEGF) 和转化生长因子 (TGF) β 的表达具有统计学意义。随着CNV增大，bFGF表达增加；相反，当膜尺寸较小时，VEGF和TGFβ表达显着。我们使用体外血管生成模型发现bFGF和VEGF共同刺激CNV的扩大，相反TGFβ抑制CNV的扩大。我们还发现缺氧会增加视网膜色素上皮（RPE）中 VEGF 的表达。这一事实可能与之前的报道一致，即低灌注可能会影响黄斑下病变处CNV的生成。此外，我们使用微孔过滤器支撑在含有 VEGF 和 bFGF 等多种细胞因子的培养基中检查了 RPE 的屏障功能。结果表明，VEGF可能影响RPE的屏障功能，但IL-1β对破坏RPE的功能具有显着的作用。