Department of Ophthalmology, Ludwig-Maximilians-University, Mathildenstrasse 8, 80336, Munich, Germany.
Graefes Arch Clin Exp Ophthalmol. 2013 Jun;251(6):1529-40. doi: 10.1007/s00417-013-2257-z. Epub 2013 Jan 18.
Posterior capsule opacification (PCO) is the most frequent complication after cataract surgery, leading to a loss of sight if untreated. Erlotinib might be of therapeutic interest as an effective target agent (selective EGF-tyrosin-kinase-1 inhibitor). In this in-vitro study, erlotinib was evaluated for ocular biocompatibility and its effect on cell proliferation, migration, 3D matrix contraction and spreading of human lens epithelial cells.
To exclude toxic concentrations, erlotinib was assessed for its biocompatibility on five different human ocular cell types in vitro by the tetrazolium dye-reduction assay (MTT) and the Live-Dead assay. To determine its effect on human lens epithelial cell (HLE-B3) proliferation, the MTT test was performed after incubation with different concentrations of erlotinib. Chemotactic migration was analyzed with the Boyden chamber assay and chemokinetic migration was assessed by time lapse microscopy. Contraction was measured by a 3D collagen type 1 matrix contraction assay, and cell spreading was determined by measuring the cell diameter on a fibronectin coated surface.
The maximum non-toxic concentration of erlotinib was determined to be 100 μM in cell culture. Erlotinib potently inhibits human lens epithelial cell proliferation, with an IC50 of about 10 μM (8.8 μM ± 0.9 μM SD; r (2) =0.94). Chemotactic migration (p=0.004) and chemokinetic migration (p=0.001) were reduced significantly in a concentration-based manner. Erlotinib prevented human lens epithelial cells from matrix contraction (p=0.001) and cell-spreading (p=0.001).
Erlotinib might become of clinical relevance for PCO prophylaxis in the future since it displayed good biocompatibility on ocular cells and mitigated human lens epithelial cell proliferation, migration, contraction, and spreading in vitro. Further studies are warranted to evaluate its potential for clinical application.
后囊混浊（PCO）是白内障手术后最常见的并发症，如果不治疗，会导致视力丧失。厄洛替尼可能具有治疗意义，因为它是一种有效的靶向药物（选择性 EGF 酪氨酸激酶-1 抑制剂）。在这项体外研究中，评估了厄洛替尼的眼生物相容性及其对人晶状体上皮细胞增殖、迁移、3D 基质收缩和铺展的影响。
为了排除毒性浓度，通过噻唑蓝染料还原试验（MTT）和 Live-Dead 试验评估了厄洛替尼对五种不同的人眼细胞类型的体外生物相容性。为了确定其对人晶状体上皮细胞（HLE-B3）增殖的影响，用 MTT 试验检测不同浓度厄洛替尼孵育后的细胞增殖。用 Boyden 室测定趋化性迁移，用延时显微镜评估趋动性迁移。通过 3D 胶原 1 基质收缩测定法测量收缩，通过测量纤维连接蛋白涂覆表面上的细胞直径来确定细胞铺展。
确定厄洛替尼在细胞培养中的最大无毒浓度为 100 μM。厄洛替尼能有效抑制人晶状体上皮细胞增殖，IC50 约为 10 μM（8.8 μM±0.9 μM SD；r（2）=0.94）。趋化性迁移（p=0.004）和趋动性迁移（p=0.001）呈浓度依赖性显著减少。厄洛替尼防止人晶状体上皮细胞基质收缩（p=0.001）和细胞铺展（p=0.001）。
厄洛替尼在眼细胞上表现出良好的生物相容性，并减轻了人晶状体上皮细胞的增殖、迁移、收缩和铺展，因此在未来可能对 PCO 的预防具有临床意义。需要进一步的研究来评估其临床应用的潜力。
