Zhang Jinyu, Lin Hongbin, Li Fengxian, Wu Kaili, Yang Shuangjian, Zhou Shiyou
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Guangzhou, China.
Front Mol Neurosci. 2023 Mar 24;16:1083850. doi: 10.3389/fnmol.2023.1083850. eCollection 2023.
Dry eye disease (DED) is a multifactorial disease with a high prevalence worldwide. Uncomfortable corneal sensations severely affect daily life in DED patients. Hence, corneal neuron injury is a vital pathogenesis in DED. Notably, endoplasmic reticulum stress (ERS) plays a role in peripheral neuron injury. However, the role of ERS in DED corneal neuron injury is still far from being clear. In this study, we established an environmental DED (eDED) model and a hyperosmotic DED model . Subsequently, trigeminal ganglion (TG) corneal neurons were retrograde labeled by WGA-Alexa Fluor 555, and fluorescence-activated cell sorting was used to collect targeted corneal neurons for RNA sequencing in mice. Our results revealed that TG corneal neuron injury but not apoptosis in DED. ERS-related genes and proteins were upregulated in TG corneal neurons of the eDED mice. ERS inhibition alleviated TG corneal neuron's ERS-related injury. Therefore, ERS-induced TG corneal neuron injury may be an important pathomechanism and provide a promising therapeutic approach to DED.
干眼症（DED）是一种多因素疾病，在全球范围内具有较高的患病率。角膜感觉不适严重影响干眼症患者的日常生活。因此，角膜神经元损伤是干眼症的一个重要发病机制。值得注意的是，内质网应激（ERS）在外周神经元损伤中起作用。然而，ERS在干眼症角膜神经元损伤中的作用仍远未明确。在本研究中，我们建立了环境性干眼症（eDED）模型和高渗性干眼症模型。随后，用WGA-Alexa Fluor 555对三叉神经节（TG）角膜神经元进行逆行标记，并使用荧光激活细胞分选技术收集靶向角膜神经元用于小鼠的RNA测序。我们的结果显示，干眼症中TG角膜神经元发生损伤但未发生凋亡。在eDED小鼠的TG角膜神经元中，与ERS相关的基因和蛋白质上调。ERS抑制减轻了TG角膜神经元的ERS相关损伤。因此，ERS诱导的TG角膜神经元损伤可能是一种重要的发病机制，并为干眼症提供了一种有前景的治疗方法。
