Dry eye disease (DED) is a multifactorial chronic inflammatory disease of the ocular surface characterized by tear film instability, hyperosmolarity, cell damage and inflammation. Hyperosmolarity is strongly established as the core mechanism of the DED. Benzalkonium chloride (BAK) - a quaternary ammonium salt commonly used in eye drops for its microbicidal properties - is well known to favor the onset of DED. Currently, little data are available regarding lipid metabolism alteration in ocular surface epithelial cells in the course of DED. Our aim was to explore the effects of benzalkonium chloride or hyperosmolarity exposure on the human corneal epithelial (HCE) cell lipidome, two different conditions used as in vitro models of DED. For this purpose, we performed a lipidomic analysis using UPLC-HRMS-ESI+/-. Our results demonstrated that BAK or hyperosmolarity induced important modifications in HCE lipidome including major changes in sphingolipids, glycerolipids and glycerophospholipids. For both exposures, an increase in ceramide was especially exhibited. Hyperosmolarity specifically induced triglyceride accumulation resulting in lipid droplet formation. Conversely, BAK induced an increase in lysophospholipids and a decrease in phospholipids. This lipidomic study highlights the lipid changes involved in inflammatory responses following BAK or hyperosmolarity exposures. Thereby, lipid research appears of great interest, as it could lead to the discovery of new biomarkers and therapeutic targets for the diagnosis and treatment of dry eye disease.

中文翻译：

---

高渗和苯扎氯铵暴露后上皮角膜细胞的脂质组学分析：干眼病的新见解。

干眼病（DED）是眼表的多因素慢性炎症性疾病，其特征在于泪膜不稳定，高渗性，细胞损伤和炎症。高渗性被强烈确立为DED的核心机制。众所周知，苯扎氯铵（BAK）是一种季铵盐，因其具有杀菌作用而常用于眼药水中，众所周知它有利于DED的发作。目前，关于DED过程中眼表上皮细胞脂质代谢改变的数据很少。我们的目的是探讨苯扎氯铵或高渗暴露对人角膜上皮（HCE）细胞脂质组的影响，这是两种不同的条件用作DED体外模型。为此，我们使用UPLC-HRMS-ESI +/-进行了脂质组分析。我们的结果表明，BAK或高渗会诱导HCE脂质组的重要修饰，包括鞘脂，甘油脂和甘油磷脂的重大变化。对于两种暴露，神经酰胺的增加尤其明显。高渗性特异地引起甘油三酸酯积累，导致脂质滴形成。相反，BAK引起溶血磷脂的增加和磷脂的减少。这项脂质组学研究强调了BAK或高渗性暴露后炎症反应中涉及的脂质变化。因此，脂质研究似乎引起了极大的兴趣，因为它可能导致发现新的生物标志物和用于治疗和治疗干眼病的治疗靶标。甘油脂和甘油磷脂。对于两种暴露，神经酰胺的增加尤其明显。高渗性特异地引起甘油三酸酯积累，导致脂质滴形成。相反，BAK引起溶血磷脂的增加和磷脂的减少。这项脂质组学研究强调了BAK或高渗性暴露后炎症反应中涉及的脂质变化。因此，脂质研究似乎引起了极大的兴趣，因为它可能导致发现新的生物标志物和用于治疗和治疗干眼病的治疗靶标。甘油脂和甘油磷脂。对于两种暴露，神经酰胺的增加尤其明显。高渗性特异地引起甘油三酸酯积累，导致脂质滴形成。相反，BAK引起溶血磷脂的增加和磷脂的减少。这项脂质组学研究强调了BAK或高渗性暴露后炎症反应中涉及的脂质变化。因此，脂质研究似乎引起了极大的兴趣，因为它可能导致发现新的生物标志物和用于治疗和治疗干眼病的治疗靶标。BAK引起溶血磷脂的增加和磷脂的减少。这项脂质组学研究强调了BAK或高渗性暴露后炎症反应中涉及的脂质变化。因此，脂质研究似乎引起了极大的兴趣，因为它可能导致发现新的生物标志物和用于治疗和治疗干眼病的治疗靶标。BAK引起溶血磷脂的增加和磷脂的减少。这项脂质组学研究强调了BAK或高渗性暴露后炎症反应中涉及的脂质变化。因此，脂质研究似乎引起了极大的兴趣，因为它可能导致发现新的生物标志物和用于治疗和治疗干眼病的治疗靶标。