Aachen Centre of Technology Transfer in Ophthalmology e.V., An-Institute RWTH Aachen University, Aachen, Germany.
J Ocul Pharmacol Ther. 2020 Dec;36(10):725-731. doi: 10.1089/jop.2020.0043. Epub 2020 Nov 11.
High-frequency applied cetalkonium chloride (CAC) and benzalkonium chloride (BAC) 0.02% did not hamper corneal healing in a living rabbit model of induced corneal erosion. In contrast, the eye irritation test (EVEIT) shows inhibition of healing for these substances. In a systematic reproduction of the experiments, we discuss the background of these differences. Excised rabbit corneas ( = 5 per group) were cultured in artificial anterior chambers (EVEIT). Four erosions were induced for each cornea before starting regular 21 installations/day over 3 days of (1) CAC containing eye drops (Cationorm), (2) 0.02% BAC. Corneal fluorescein staining, quantification of glucose-/lactate consumption, and histology were performed. BAC 0.02% treated corneas showed increased epithelial lesions from 10.13 ± 0.65 mm to 10 ± 0.8 mm on day 0, to 86.82 ± 5.18 mm ( < 0.0001) by day 3. After a trend toward smaller lesions for CAC on day 1, erosion sizes increased significantly by day 3 from 9.82 ± 0.30 mm to 29.51 ± 16.87 mm ( < 0.05). For 1 cornea, corneal erosions nearly disappeared on day 3 (0.89 mm). Corneal lactate increased significantly for BAC and CAC, whereas glucose concentrations were unchanged. Histology revealed disintegration of the corneal structures for both compounds. The data underline the EVEIT as a predictive toxicity test to show side effects in a time-compressed manner. The consistency of these predictions was previously demonstrated by the EVEIT for BAC, phosphate buffer, and others. The EVEIT is suited for a chronic application prediction of tolerability and toxic side effects of eye drops in particular, and other chemicals in general.
高频应用的西他氯铵（CAC）和苯扎氯铵（BAC）0.02% 不会阻碍活体兔诱导性角膜侵蚀模型中的角膜愈合。相比之下，眼刺激试验（EVEIT）显示这些物质会抑制愈合。在系统复制这些实验的基础上，我们讨论了这些差异的背景。 每组（ = 5 个）切除的兔角膜在人工前房（EVEIT）中培养。在开始每天 21 次安装（1）含 CAC 的滴眼液（Cationorm），（2）0.02% BAC 之前，每个角膜诱导 4 次侵蚀。进行角膜荧光素染色、葡萄糖/乳酸消耗定量和组织学检查。 BAC 0.02% 处理的角膜显示上皮病变从第 0 天的 10.13 ± 0.65 mm 增加到 10 ± 0.8 mm，到第 3 天增加到 86.82 ± 5.18 mm（ < 0.0001）。CAC 在第 1 天的病变趋势较小，第 3 天的侵蚀大小从 9.82 ± 0.30 mm 显著增加到 29.51 ± 16.87 mm（ < 0.05）。对于 1 个角膜，角膜侵蚀在第 3 天几乎消失（0.89 mm）。BAC 和 CAC 引起的角膜乳酸明显增加，而葡萄糖浓度不变。组织学显示两种化合物的角膜结构解体。 这些数据强调了 EVEIT 作为一种预测毒性试验，能够以时间压缩的方式显示副作用。EVEIT 以前已经通过 BAC、磷酸盐缓冲液和其他物质的 EVEIT 证明了这些预测的一致性。EVEIT 特别适合预测滴眼液的慢性应用耐受性和毒性副作用，以及其他一般化学物质的毒性副作用。
