De Piano Maria, Cacciamani Andrea, Balzamino Bijorn Omar, Scarinci Fabio, Cosimi Pamela, Cafiero Concetta, Ripandelli Guido, Micera Alessandra
Research and Development Laboratory for Biochemical, Molecular and Cellular Applications in Ophthalmological Science, IRCCS-Fondazione Bietti, 00184 Rome, Italy.
Surgical Retina Research Unit, IRCCS-Fondazione Bietti, 00184 Rome, Italy.
Biomolecules. 2023 Aug 29;13(9):1328. doi: 10.3390/biom13091328.
Inflammatory, vasculogenic, and profibrogenic factors have been previously reported in vitreous (VH) and aqueous (AH) humors in myopic patients who underwent cataract surgery. In light of this, we selected some mediators for AH and anterior-capsule-bearing lens epithelial cell (AC/LEC) analysis, and AH expression was correlated with LEC activation (epithelial-mesenchymal transition and EMT differentiation) and axial length (AL) elongation. In this study, AH (97; 41M/56F) and AC/LEC samples (78; 35M/43F) were collected from 102 patients who underwent surgery, and biosamples were grouped according to AL elongation. Biomolecular analyses were carried out for AH and LECs, while microscopical analyses were restricted to whole flattened AC/LECs. The results showed increased levels of interleukin (IL)-6, IL-8, and angiopoietin-2 (ANG)-2 and decreased levels of vascular endothelium growth factor (VEGF)-A were detected in AH depending on AL elongation. LECs showed EMT differentiation as confirmed by the expression of smooth muscle actin (α-SMA) and transforming growth factor (TGF)-βR1/TGFβ isoforms. A differential expression of IL-6R/IL-6, IL-8R/IL-8, and VEGF-R1/VEGF was observed in the LECs, and this expression correlated with AL elongation. The higher VEGF-A and lower VEGF-D transcript expressions were detected in highly myopic LECs, while no significant changes were monitored for VEGF-R transcripts. In conclusion, these findings provide a strong link between the AH protein signature and the EMT phenotype. Furthermore, the low VEGF-A/ANG-2 and the high VEGF-A/VEGF-D ratios in myopic AH might suggest a specific inflammatory and profibrogenic pattern in high myopia. The highly myopic AH profile might be a potential candidate for rating anterior chamber inflammation and predicting retinal distress at the time of cataract surgery.
先前有报道称,在接受白内障手术的近视患者的玻璃体(VH)和房水(AH)中存在炎症、血管生成和促纤维化因子。鉴于此,我们选择了一些介质进行房水和含前囊的晶状体上皮细胞(AC/LEC)分析,并且房水表达与LEC激活(上皮-间质转化和EMT分化)以及眼轴长度(AL)延长相关。在本研究中,从102例接受手术的患者中收集了房水样本(97份;41例男性/56例女性)和AC/LEC样本(78份;35例男性/43例女性),并根据眼轴长度延长对生物样本进行分组。对房水和LEC进行了生物分子分析,而显微镜分析仅限于整个扁平的AC/LEC。结果显示,根据眼轴长度延长情况,房水中白细胞介素(IL)-6、IL-8和血管生成素-2(ANG)-2水平升高,而血管内皮生长因子(VEGF)-A水平降低。LEC表现出EMT分化,这通过平滑肌肌动蛋白(α-SMA)和转化生长因子(TGF)-βR1/TGFβ异构体的表达得到证实。在LEC中观察到IL-6R/IL-6、IL-8R/IL-8和VEGF-R1/VEGF的差异表达,并且这种表达与眼轴长度延长相关。在高度近视LEC中检测到较高的VEGF-A和较低的VEGF-D转录物表达,而VEGF-R转录物未监测到显著变化。总之,这些发现为房水蛋白特征与EMT表型之间提供了强有力的联系。此外,近视房水中低VEGF-A/ANG-2和高VEGF-A/VEGF-D比值可能表明高度近视中存在特定的炎症和促纤维化模式。高度近视房水特征可能是评估前房炎症和预测白内障手术时视网膜病变的潜在候选指标。