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  2. The ROS/AKT/S6K axis induces corneal epithelial dysfunctions under LED blue light exposure

The ROS/AKT/S6K axis induces corneal epithelial dysfunctions under LED blue light exposure

  • Ecotoxicol Environ Saf. 2024 Nov 15:287:117345. doi: 10.1016/j.ecoenv.2024.117345.
Le Jin 1 Qianjie Yang 1 Jiafeng Li 2 Xiang Li 1 Yutong Xia 1 Zhitong Chen 1 Yingying Wen 1 Liyin Wang 1 Xiawei Wang 1 Jianping Tong 3 Ye Shen 4 Kuangqi Chen 5
Affiliations

Affiliations

  • 1 Department of Ophthalmology, the First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, China.
  • 2 Department of Orthopedic Surgery, the First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, China.
  • 3 Department of Ophthalmology, the First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, China. Electronic address: idrtong@zju.edu.cn.
  • 4 Department of Ophthalmology, the First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, China. Electronic address: idrshen@zju.edu.cn.
  • 5 Department of Ophthalmology, the First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, China; School of Ophthalmology, Shandong First Medical University, Jinan, Shandong, China; Eye Hospital of Shandong First Medical University (Shandong Eye Hospital), Eye Institute of Shandong First Medical University, State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Jinan, Shandong, China, Shandong First Medical University, Jinan, Shandong, China. Electronic address: 3160105142@zju.edu.cn.
Abstract

In recent years, concerns have escalated regarding eye health problems arising from Light-emitting diode (LED), which emits high-energy blue light (BL), potentially causing corneal epithelial dysfunctions (CEpD). Nevertheless, the mechanisms underlying this damage remain poorly comprehended. This study endeavors to explore the specific mechanisms through which BL exposure induces CEpD. The study carried out diverse assays and treatments to investigate the toxicological effects of BL exposure. 48 hours (h) of 440 nm of BL exposure decreased the migration of human corneal epithelial cells (hCEpCs) while augmenting Reactive Oxygen Species (ROS) production and Apoptosis. RNA-Sequencing and bioinformatic analysis indicated that cellular oxidation and reduction equilibrium, wound healing, the positive regulation of the apoptotic process, and the Phosphoinositide 3-kinase (PI3K)/Akt pathway were significantly influenced by BL exposure. Treatment with N-acetylcysteine (NAC), a ROS scavenger, restored cell viability and Akt/S6 kinase (S6K) activation, suggesting the involvement of ROS in BL-induced damage. NAC also reversed BL-induced Apoptosis and migration. Blocking Akt/S6K replicated detrimental effects, while pre-treatment with SC79 (SC), an Akt Activator, alleviated the changes caused by BL exposure in hCEpCs. Furthermore, in mice, the combination of Akt inhibition and BL exposure led to CEpD. However, treatment with SC and NAC restored CEpD caused by BL exposure. These results imply that the regulation of the ROS/PI3K/Akt/S6K axis is implicated in BL-induced CEpD. Collectively, this study offers insights into the molecular mechanisms of BL-induced CEpD and proposes targeting the ROS/PI3K/Akt/S6K cascade as a potential therapeutic approach. The findings contribute to ocular health knowledge and establish the basis for developing interventions to safeguard the cornea from the detrimental effects of excessive BL exposure.

Keywords

Blue light; Corneal epithelial dysfunctions; Light-emitting diode (LED); PI3K/AKT signalling; Reactive oxygen species (ROS).

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