Choroidal neovascularization (CNV) is a major cause of blindness in patients with age-related macular degeneration (AMD). Overexpression of vascular endothelial growth factor (VEGF), a potent angiogenic protein, by retinal pigment epithelial (RPE) cells is a key stimulator of CNV. Mechanical stress occurs during different stages of AMD and is a possible inducer of VEGF expression in RPE cells. However, robust and realistic approaches to studying acute and chronic mechanical stress under various AMD stages do not exist. The majority of previous work has studied cyclic stretching of RPE cells grown on flexible substrates, but an ideal model must be able to mimic localized and continuous stretching of the RPE as would occur in AMD in vivo. To bridge this gap, we developed two in vitro devices to model chronic and acute mechanical stress on RPE cells during different stages of AMD. In one device, high levels of continuous mechanical stress were applied to focal regions of the RPE monolayer by stretching the underlying silicon substrate to study the role of chronic mechanical stimulation. In the second device, RPE cells were grown on porous plastic substrates and acute stress was studied by stretching small areas. Using these devices, we studied the effect of mechanical stress on VEGF expression in RPE cells. Our results suggest that mechanical stress in RPE cells induces VEGF expression and promotes in vitro angiogenesis. These results confirm the hypothesis that mechanical stress is involved in the initiation and progression of CNV.

中文翻译：

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研究视网膜色素上皮细胞急性和慢性机械应力的新型设备

脉络膜新生血管形成（CNV）是年龄相关性黄斑变性（AMD）患者失明的主要原因。视网膜色素上皮（RPE）细胞过度表达血管内皮生长因子（VEGF）是一种有效的血管生成蛋白，是CNV的关键刺激因子。机械应力发生在AMD的不同阶段，并且可能是RPE细胞中VEGF表达的诱导物。但是，尚不存在在各种AMD阶段研究急性和慢性机械应力的有效方法。先前的大部分工作都研究了在柔性基板上生长的RPE细胞的循环拉伸，但是理想的模型必须能够模拟RPE的局部和连续拉伸，就像在AMD体内发生的那样。为了弥合这一差距，我们在体外开发了两种在AMD的不同阶段对RPE细胞的慢性和急性机械应力进行建模的设备。在一种设备中，通过拉伸下面的硅基板，将高水平的连续机械应力施加到RPE单层的焦点区域，以研究慢性机械刺激的作用。在第二个设备中，RPE细胞在多孔塑料基板上生长，并通过拉伸小面积研究了急性应力。使用这些设备，我们研究了机械应力对RPE细胞中VEGF表达的影响。我们的结果表明，RPE细胞中的机械应力可诱导VEGF表达并促进体外血管生成。这些结果证实了机械应力与CNV的发生和发展有关的假设。