Clinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain; Facultade de Óptica e Optometría, Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain.
Clinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
Exp Eye Res. 2020 Nov;200:108211. doi: 10.1016/j.exer.2020.108211. Epub 2020 Sep 2.
The main purpose of this study is to evaluate the diagnostic role of Toll-like receptors 2 (TLR2) and 4 (TLR4) expression in corneal and conjunctival epithelial cells of eyes with pellucid marginal degeneration (PMD) compared to keratoconus patients (KC) and control subjects. A prospective case-control study in 29 PMD eyes, 109 KC eyes and 72 healthy eyes was done. All participants were subjected to a clinical, topographic, aberrometric and tomographic exam with extraction of corneal and conjunctival epithelial cells through scraping. The TLR2 and TLR4 expression was measured with flow cytometry. Receiver operating characteristic (ROC) curve analysis was used to determine the most appropriate cutoff point for predicting the risk of PMD and KC. Correlations between TLR2/TLR4 expression and the severity of PMD/KC were evaluated. A TLRs follow-up review was made 19 ± 4 months after to the first review. As result, mean expression of TLR2 and TLR4 in both corneal and conjunctival epithelial cells was significantly higher in eyes with corneal ectasia (PMD and KC) than in control eyes (all p < 0.05). Conjunctival TLR4 expression showed the highest capacity to diagnose the existence of PMD (odd ratio 42.84; 95% confidence interval:6.20-296.20; p < 0.0001) after adjusting by eye rubbing and steeper corneal meridian. Moreover, we found an association between the TLR2/TLR4 overexpression with the severity of the PMD and KC measured by corneal topographic, aberrometric and tomographic quantitative parameters (all p < 0.05). Differences on TLR2/TLR4 expression between study groups were maintained during the follow-up period. In conclusion, the TLR2/TLR4 overexpression in corneal and conjunctival epithelial cells of PMD and KC patients compared to healthy control subjects have demonstrated their role as diagnostic target in both corneal ectatic disorders.
本研究的主要目的是评估 Toll 样受体 2(TLR2)和 4(TLR4)在角膜和结膜上皮细胞中的表达在透明边缘变性(PMD)眼中的诊断作用,与圆锥角膜患者(KC)和对照组相比。对 29 只 PMD 眼、109 只 KC 眼和 72 只健康眼进行了前瞻性病例对照研究。所有参与者均接受了临床、地形学、像差和断层扫描检查,并通过刮擦提取角膜和结膜上皮细胞。通过流式细胞术测量 TLR2 和 TLR4 的表达。使用接收者操作特征(ROC)曲线分析确定预测 PMD 和 KC 风险的最佳截断点。评估 TLR2/TLR4 表达与 PMD/KC 严重程度之间的相关性。在第一次检查后 19±4 个月进行了 TLRs 随访。结果,角膜扩张(PMD 和 KC)眼的角膜和结膜上皮细胞中 TLR2 和 TLR4 的平均表达明显高于对照组(均 p<0.05)。调整眼部摩擦和更陡的角膜子午线后,结膜 TLR4 表达显示出诊断 PMD 存在的最高能力(优势比 42.84;95%置信区间:6.20-296.20;p<0.0001)。此外,我们发现 TLR2/TLR4 过表达与角膜地形图、像差和断层扫描定量参数测量的 PMD 和 KC 的严重程度之间存在关联(均 p<0.05)。在随访期间,研究组之间 TLR2/TLR4 表达的差异得以维持。总之,与健康对照组相比,PMD 和 KC 患者的角膜和结膜上皮细胞中 TLR2/TLR4 的过表达表明它们在两种角膜扩张性疾病中具有作为诊断靶标的作用。