Li Senmao, Xie Jingbin, Xiang Jiayan, Yan Ruyu, Liu Jiangman, Fan Qiwei, Lu Liyuan, Wu Jiaxin, Liu Jun, Xue Yunxia, Fu Ting, Li Zhijie
Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
International Ocular Surface Research Center, Institute of Ophthalmology and Key Laboratory for Regenerative Medicine, Jinan University Medical School, Guangzhou, China.
Invest Ophthalmol Vis Sci. 2025 Apr 1;66(4):40. doi: 10.1167/iovs.66.4.40.
To investigate the impact of corneal sensory nerve injury on lacrimal gland function, focusing on mechanisms involving the superior salivatory nucleus (SSN), circadian rhythm disruption, immune microenvironment alterations, and the potential for neural regeneration.
A murine model of corneal sensory nerve injury was used to assess lacrimal gland function, with tear secretion measured using the phenol red thread test. Transcriptomic analysis of lacrimal glands examined circadian rhythm and immune-related gene expression. Basic fibroblast growth factor (bFGF) was used to promote corneal nerve regeneration, and its effects on tear secretion and nerve repair were evaluated.
Corneal nerve injury resulted in a 35% reduction in tear secretion and significantly impaired SSN activity, as evidenced by a 31% decrease in c-FOS-positive neurons in choline acetyltransferase (ChAT)-expressing neurons. Transcriptomic analysis revealed significant downregulation of immune-related pathways, including Toll-like receptor (TLR), NOD-like receptor (NLR), and T-cell receptor signaling. Circadian rhythm gene expression exhibited phase shifts, with a 2.13-hour delay in peak expression and a substantial change in the number and types of rhythmic genes, which were enriched in different signaling pathways. The bFGF treatment restored tear secretion by 22% and promoted nerve regeneration, although nerve fiber density remained 74% lower than that of controls.
Corneal sensory nerve injury disrupts both central and peripheral circadian clock functions in the lacrimal gland, leading to reduced tear secretion and immune dysregulation. These findings highlight the novel role of circadian rhythms and neural-immune interactions in lacrimal gland dysfunction. Neural regeneration strategies, such as bFGF, offer therapeutic potential for dry eye syndrome, providing new directions for clinical intervention.
研究角膜感觉神经损伤对泪腺功能的影响，重点关注涉及上涎核（SSN）、昼夜节律紊乱、免疫微环境改变以及神经再生潜力的机制。
使用角膜感觉神经损伤的小鼠模型评估泪腺功能，通过酚红棉线试验测量泪液分泌。对泪腺进行转录组分析，检测昼夜节律和免疫相关基因的表达。使用碱性成纤维细胞生长因子（bFGF）促进角膜神经再生，并评估其对泪液分泌和神经修复的影响。
角膜神经损伤导致泪液分泌减少35%，并显著损害SSN活性，这在胆碱乙酰转移酶（ChAT）表达神经元中c-FOS阳性神经元减少31%中得到证实。转录组分析显示免疫相关途径显著下调，包括Toll样受体（TLR）、NOD样受体（NLR）和T细胞受体信号通路。昼夜节律基因表达出现相位偏移，峰值表达延迟2.13小时，节律性基因的数量和类型发生显著变化，这些基因在不同信号通路中富集。bFGF治疗使泪液分泌恢复了22%，并促进了神经再生，尽管神经纤维密度仍比对照组低74%。
角膜感觉神经损伤破坏了泪腺的中枢和外周昼夜节律功能，导致泪液分泌减少和免疫失调。这些发现突出了昼夜节律和神经-免疫相互作用在泪腺功能障碍中的新作用。神经再生策略，如bFGF，为干眼症综合征提供了治疗潜力，为临床干预提供了新方向。
