Center for Bioengineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
Integr Biol (Camb). 2013 Mar;5(3):474-80. doi: 10.1039/c3ib20259c.
Fluid dynamics play a fundamental role in the development of diabetic retinopathy, one of the leading causes of blindness in the Western world, affecting over 4 million people in the US alone. The disease is defined by microaneurysms, local expansions of capillaries that disturb the hemodynamic forces experienced by the endothelium leading to dysfunction, leakage and edema. Here we present a method to identify microaneurysms with a high risk of leakage based on a critical ratio of microaneurysm to vessel diameter. We derive this non-dimensional parameter from an analytical solution and generalize it using experimentally validated numerical methods. We show that this non-dimensional parameter defines the shear force experienced by endothelial cells, below which endothelial dysfunction is evident in vivo. Our results demonstrate the involvement of vWF in diabetic retinopathy, and explain a perceived disconnect between microaneurysm size and leakage. This method will allow experts to treat microaneurysms poising a high-risk of leakage, prior to edema, minimizing damage and saving vision.
流体动力学在糖尿病性视网膜病变的发展中起着至关重要的作用,这种疾病是西方世界导致失明的主要原因之一,仅在美国就影响了超过 400 万人。该疾病的特征是微动脉瘤,即毛细血管的局部扩张,扰乱了内皮细胞所经历的血液动力学力,导致功能障碍、渗漏和水肿。在这里,我们提出了一种基于微动脉瘤与血管直径的临界比来识别具有高渗漏风险的微动脉瘤的方法。我们从解析解中推导出这个无量纲参数,并使用经过实验验证的数值方法对其进行推广。我们表明,这个无量纲参数定义了内皮细胞所经历的剪切力,低于该值,内皮功能障碍在体内就会显现。我们的研究结果表明 vWF 在糖尿病性视网膜病变中的作用,并解释了微动脉瘤大小和渗漏之间的一种被认为是脱节的现象。这种方法将使专家能够在水肿发生之前治疗具有高渗漏风险的微动脉瘤,从而最小化损伤并保护视力。