Chang William, Lajko Michelle, Fawzi Amani A
Department of Ophthalmology, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States of America.
PLoS One. 2018 Jan 19;13(1):e0191285. doi: 10.1371/journal.pone.0191285. eCollection 2018.
To characterize the relationship between endothelin-1 and fibrosis in epiretinal membranes in proliferative diabetic retinopathy and explore the role of endothelial-mesenchymal transition in these membranes.
Membranes were obtained from eyes undergoing pars plana vitrectomy for complicated proliferative diabetic retinopathy or idiopathic epiretinal membrane. Through standard immunohistochemical techniques, we labeled membranes to explore the distribution of endothelin-1 and endothelin receptor B, comparing proliferative diabetic retinopathy and idiopathic epiretinal membranes. In addition, membranes were also labeled with markers for fibroblasts, endothelial, and glial cells and studied with confocal laser scanning microscopy. The intensity of endothelin-1 labeling was quantified using standard image analysis software.
Fourteen membranes were included in the analysis, nine from eyes with proliferative diabetic retinopathy and five idiopathic membranes. Flatmount diabetic membranes showed co-localization of endothelin-1 with S100A4 and CD31. Immunohistochemistry and quantitative analysis of cross-sectional membranes showed significantly higher endothelin-1 labeling in proliferative diabetic retinopathy membranes compared to idiopathic membranes (p<0.05). Diabetic membranes showed more elements staining positive for S100A4 compared to idiopathic membranes.
Epiretinal membrane formation in proliferative diabetic retinopathy involves higher tissue levels of endothelin-1 and fibroblastic activity. Furthermore, endothelin-1, endothelial and fibroblastic staining appear to be correlated, suggestive of endothelial-to-mesenchymal transition in proliferative diabetic retinopathy.
明确增殖性糖尿病视网膜病变视网膜前膜中内皮素-1与纤维化之间的关系,并探讨内皮-间充质转化在这些膜中的作用。
从因复杂性增殖性糖尿病视网膜病变或特发性视网膜前膜而接受玻璃体切割术的眼中获取视网膜前膜。通过标准免疫组织化学技术,标记视网膜前膜以探究内皮素-1和内皮素受体B的分布,比较增殖性糖尿病视网膜病变和特发性视网膜前膜。此外,还用成纤维细胞、内皮细胞和神经胶质细胞的标志物标记视网膜前膜,并采用共聚焦激光扫描显微镜进行研究。使用标准图像分析软件对内皮素-1标记强度进行定量分析。
14个视网膜前膜纳入分析,其中9个来自增殖性糖尿病视网膜病变患者的眼,5个为特发性视网膜前膜。糖尿病视网膜前膜铺片显示内皮素-1与S100A4和CD31共定位。视网膜前膜横断面的免疫组织化学和定量分析显示,增殖性糖尿病视网膜病变视网膜前膜中的内皮素-1标记显著高于特发性视网膜前膜(p<0.05)。与特发性视网膜前膜相比,糖尿病视网膜前膜显示更多S100A4染色阳性成分。
增殖性糖尿病视网膜病变中视网膜前膜的形成涉及更高水平的组织内皮素-1和成纤维细胞活性。此外,内皮素-1、内皮细胞和成纤维细胞染色似乎相关,提示增殖性糖尿病视网膜病变中存在内皮-间充质转化。