Vega Rocío, Carretero Manuel, Bonilla Luis L
Department of Mathematics, Gregorio Millán Institute, Fluid Dynamics, Nanoscience and Industrial Mathematics, Universidad Carlos III de Madrid, 28911 Leganés, Spain.
Biomedicines. 2021 Feb 22;9(2):224. doi: 10.3390/biomedicines9020224.
Age-related macular degeneration (AMD) may cause severe loss of vision or blindness, particularly in elderly people. Exudative AMD is characterized by the angiogenesis of blood vessels growing from underneath the macula, crossing the blood-retina barrier (which comprises Bruch's membrane (BM) and the retinal pigmentation epithelium (RPE)), leaking blood and fluid into the retina and knocking off photoreceptors. Here, we simulate a computational model of angiogenesis from the choroid blood vessels via a cellular Potts model, as well as BM, RPE cells, drusen deposits and photoreceptors. Our results indicate that improving AMD may require fixing the impaired lateral adhesion between RPE cells and with BM, as well as diminishing Vessel Endothelial Growth Factor (VEGF) and Jagged proteins that affect the Notch signaling pathway. Our numerical simulations suggest that anti-VEGF and anti-Jagged therapies could temporarily halt exudative AMD while addressing impaired cellular adhesion, which could be more effective over a longer time-span.
年龄相关性黄斑变性(AMD)可能导致严重的视力丧失或失明,尤其是在老年人中。渗出性AMD的特征是血管从黄斑下方生长,穿过血视网膜屏障(由布鲁赫膜(BM)和视网膜色素上皮(RPE)组成),将血液和液体渗漏到视网膜中并破坏光感受器。在这里,我们通过细胞Potts模型以及BM、RPE细胞、玻璃膜疣沉积物和光感受器模拟脉络膜血管生成的计算模型。我们的结果表明,改善AMD可能需要修复RPE细胞与BM之间受损的侧向粘附,以及减少影响Notch信号通路的血管内皮生长因子(VEGF)和锯齿蛋白。我们的数值模拟表明,抗VEGF和抗锯齿疗法可以在解决细胞粘附受损的同时暂时阻止渗出性AMD,这在更长的时间跨度内可能更有效。