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

老年性黄斑变性（AMD）患者由于黄斑下脉络膜新生（CNV）而产生不同程度的黄斑下出血、渗出、视网膜脱离等。目前还没有安全稳定治疗该病的报道，患者被迫限制生活质量。其中一个原因是新血管膜生成的机制尚不清楚。我们检测了AMD患者CNV中的mRNA表达，并将其与来自增殖性玻璃体视网膜病变（PVR）和糖尿病视网膜病变（PDR）患者的其他增生性膜的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的表达有统计学意义。随着CNV的增大，bFGF的表达增加，相反，在膜小尺寸时，VEGF和TGF β的表达显著。在体外血管生成模型中，我们发现bFGF和VEGF共同刺激CNV的增大，而TGF β则抑制CNV的增大。我们还发现缺氧增加了视网膜色素上皮（RPE）中VEGF的表达。这一事实可能与先前的报道一致，即低灌注可能影响黄斑下病变处CNV的产生。此外，我们在含有多种细胞因子（包括VEGF和bFGF）的培养基中使用微孔过滤器支持来检测RPE的屏障功能。结果表明，VEGF可能影响RPE的屏障功能，但白细胞介素-1 β对RPE的破坏作用明显。

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.