Dinice Lucia, Cacciamani Andrea, Esposito Graziana, Taurone Samanta, Carletti Raffaella, Ripandelli Guido, Artico Marco, Micera Alessandra
Research Laboratories in Ophthalmology, IRCCS-Fondazione Bietti, Via Santo Stefano Rotondo, 6, 00184, Rome, Italy.
Retinal Unit, IRCCS-Fondazione Bietti, Rome, Italy.
Graefes Arch Clin Exp Ophthalmol. 2020 Jul;258(7):1503-1513. doi: 10.1007/s00417-020-04685-w. Epub 2020 Apr 10.
To investigate osteopontin (OPN) expression in vitreous and in related idiopathic epiretinal membranes (ERMs), with respect to VEGF-A, IL8, MIP1α, IL6, and IL33, and correlate OPN expression with disease staging.
Fifteen (15) vitreous and allied ERMs were collected at the time of therapeutic vitreoretinal surgery. Additional 5 vitreous and 10 ERMs (historical collection) were used. Biochemical and molecular analysis of OPN was performed in clear vitreous, vitreal pelleted cells, and ERMs. Double-immunofluorescence analysis (OPN - GFAP and OPN - αSMA) was performed on paraffin and whole-mounted ERMs. Vitreal OPN levels were correlated to those of VEGF-A, IL8, MIP1α, IL6, and IL33.
High OPN levels were observed in vitreal samples, and OPN transcripts were amplified in vitreal cells and related ERMs. OPN immunoreactivity was found in ERMs, mainly in GFAP-bearing (Muller cells) and to a less extend in αSMA-expressing (myofibroblasts) cells. OPN levels were highest at early stages of ERM formation and positively correlated to VEGF-A and MIP1α.
High OPN levels in vitreous, OPN transcripts in vitreal cells/ERMs, OPN immunoreactivity in activated Müller cells and contractile myofibroblasts, as well as the correlation with VEGF-A and MIP1α fulfill the potential involvement of OPN in both inflammation and tissue remodeling that takes part in vitreoretinal interface disorders. The highest OPN levels at early stages of ERM formation would prospect OPN as a potential biomarker for disease severity.
研究骨桥蛋白（OPN）在玻璃体及相关特发性视网膜前膜（ERM）中的表达，以及与血管内皮生长因子A（VEGF - A）、白细胞介素8（IL8）、巨噬细胞炎性蛋白1α（MIP1α）、白细胞介素6（IL6）和白细胞介素33（IL33）的关系，并将OPN表达与疾病分期相关联。
在治疗性玻璃体视网膜手术时收集15份玻璃体及相关ERM样本。另外使用5份玻璃体样本和10份ERM样本（历史收集样本）。对清亮玻璃体、玻璃体沉淀细胞及ERM进行OPN的生化和分子分析。在石蜡包埋和整装的ERM上进行双重免疫荧光分析（OPN - 胶质纤维酸性蛋白（GFAP）和OPN - α平滑肌肌动蛋白（αSMA））。将玻璃体中OPN水平与VEGF - A、IL8、MIP1α、IL6和IL33的水平进行关联分析。
在玻璃体样本中观察到高OPN水平，并且在玻璃体细胞及相关ERM中扩增出OPN转录本。在ERM中发现OPN免疫反应性，主要存在于表达GFAP的（Muller细胞），在表达αSMA的（肌成纤维细胞）细胞中程度较轻。OPN水平在ERM形成的早期阶段最高，并且与VEGF - A和MIP1α呈正相关。
玻璃体中高OPN水平、玻璃体细胞/ERM中的OPN转录本、活化的Muller细胞和收缩性肌成纤维细胞中的OPN免疫反应性，以及与VEGF - A和MIP1α的相关性，表明OPN可能参与了玻璃体视网膜界面疾病中炎症和组织重塑过程。ERM形成早期阶段最高的OPN水平预示OPN可能是疾病严重程度的潜在生物标志物。
