Huang Shenzhen, Zhang Wenxiao, Ba Mengru, Xuan Shuting, Huang Duliurui, Qi Di, Pei Xiaoting, Lu Dingli, Li Zhijie
Department of Ophthalmology, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China.
Henan Eye Institute, Henan Eye Hospital, People's Hospital of Henan University, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China.
Invest Ophthalmol Vis Sci. 2025 Jan 2;66(1):12. doi: 10.1167/iovs.66.1.12.
Chronic jet lag (CJL) is known to disrupt circadian rhythms, which regulate various physiological processes, including ocular surface homeostasis. However, the specific effects of CJL on lacrimal gland function and the underlying cellular mechanisms remain poorly understood.
A CJL model was established using C57BL/6J mice. Extraorbital lacrimal glands (ELGs) were collected at 3-hour intervals for RNA extraction and high-throughput RNA sequencing. Circadian transcriptomic profiles were analyzed, and functional annotations were performed. Hydrogen peroxide levels and total antioxidant capacity in tear fluid were measured using chemometric assays. Immunofluorescence was used to assess cell proliferation, apoptosis, immune cell infiltration in ELGs, and reactive oxygen species (ROS) accumulation. The potential therapeutic effects of alpha-lipoic acid (ALA) on CJL-induced oxidative stress and pathological changes in ELGs were also investigated.
CJL significantly disrupted locomotor activity, altered body temperature rhythms, and modified diurnal oscillations in ELGs. Transcriptomic analysis revealed extensive changes in rhythmic gene expression, phase shifts, and pathway clustering in response to CJL. The disruption of the core circadian clock transcription was associated with ELG hyperproliferation and increased ROS accumulation. tert-Butyl hydroperoxide promoted ELG cell proliferation, and ALA effectively reduced ROS levels and mitigated CJL-induced hyperproliferation.
These findings uncover novel molecular pathways affected by CJL and highlight the potential of antioxidant therapies, such as ALA, in preserving ocular surface health under conditions of circadian rhythm disruption.
已知慢性时差反应（CJL）会扰乱昼夜节律，而昼夜节律调节包括眼表稳态在内的各种生理过程。然而，CJL对泪腺功能的具体影响及其潜在的细胞机制仍知之甚少。
使用C57BL/6J小鼠建立CJL模型。每隔3小时收集眶外泪腺（ELG）用于RNA提取和高通量RNA测序。分析昼夜转录组图谱并进行功能注释。使用化学计量学测定法测量泪液中的过氧化氢水平和总抗氧化能力。采用免疫荧光法评估ELG中的细胞增殖、凋亡、免疫细胞浸润以及活性氧（ROS）积累。还研究了α-硫辛酸（ALA）对CJL诱导的氧化应激和ELG病理变化的潜在治疗作用。
CJL显著扰乱运动活动，改变体温节律，并改变ELG中的昼夜振荡。转录组分析显示，响应CJL，节律性基因表达、相移和通路聚类发生了广泛变化。核心昼夜节律时钟转录的破坏与ELG过度增殖和ROS积累增加有关。叔丁基过氧化氢促进ELG细胞增殖，而ALA有效降低ROS水平并减轻CJL诱导的过度增殖。
这些发现揭示了受CJL影响的新分子途径，并突出了抗氧化疗法（如ALA）在昼夜节律紊乱条件下保护眼表健康的潜力。
