Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland.
Acta Ophthalmol. 2022 Aug;100(5):e1153-e1162. doi: 10.1111/aos.15051. Epub 2021 Oct 26.
It has been hypothesized that epithelial-mesenchymal transition (EMT) may occur in the retinal pigment epithelium of advanced stage age-related macular degeneration (AMD). Various serum and plasma growth factors and inflammatory mediators have been linked to AMD. We were interested in finding out whether systemic levels of EMT-associated markers were altered in the serum of wet AMD patients. Serum biomarkers associated with the various pathological processes of AMD may present an avenue towards identifying and characterizing the birth mechanisms of wet AMD, its progression and severity, paving the way towards the application of precision medicine.
We chose to measure the serum levels of known biomarkers of EMT - EGF (epidermal growth factor), ET-1 (endothelin 1), IL-8 (interleukin 8), TGF-β1 and TGF-β2 (transforming growth factor-beta 1 and 2) and VEGF-A (vascular endothelial growth factor A) - using enzyme-linked immunosorbent assays. We measured them from 71 Finnish wet AMD patients who were receiving intravitreal anti-VEGF-A injection treatments, as well as 64 age-adjusted controls.
We found significantly elevated levels of ET-1, IL-8 and TGF-β2 in the serums of wet AMD patients.
ET-1, IL-8 and TGF-β2 appear to be useful serum biomarkers in understanding active wet AMD. However, we cannot conclude that local retinal EMT-processes could be observed from the corresponding systemic serum biomarkers in patients undergoing anti-VEGF-A treatments.
有人假设,在晚期年龄相关性黄斑变性(AMD)的视网膜色素上皮中可能发生上皮-间充质转化(EMT)。各种血清和血浆生长因子和炎症介质与 AMD 有关。我们有兴趣了解湿性 AMD 患者的血清中 EMT 相关标志物的系统水平是否发生改变。与 AMD 各种病理过程相关的血清生物标志物可能为确定和描述湿性 AMD 的发生机制、其进展和严重程度提供了一种途径,为精准医学的应用铺平了道路。
我们选择使用酶联免疫吸附测定法来测量已知 EMT 标志物——EGF(表皮生长因子)、ET-1(内皮素 1)、IL-8(白细胞介素 8)、TGF-β1 和 TGF-β2(转化生长因子-β 1 和 2)和 VEGF-A(血管内皮生长因子 A)——的血清水平。我们从 71 名接受玻璃体内抗 VEGF-A 注射治疗的芬兰湿性 AMD 患者以及 64 名年龄匹配的对照者中测量了这些标志物。
我们发现湿性 AMD 患者的血清中 ET-1、IL-8 和 TGF-β2 水平显著升高。
ET-1、IL-8 和 TGF-β2 似乎是理解活动性湿性 AMD 的有用血清生物标志物。然而,我们不能得出结论,即正在接受抗 VEGF-A 治疗的患者中,相应的系统血清生物标志物可以观察到局部视网膜 EMT 过程。