Pei Xiaoting, Ba Mengru, Yang Tingting, Xuan Shuting, Huang Duliurui, Qi Di, Lu Dingli, Huang Shenzhen, Li Zhijie
Henan Eye Institute, Henan Eye Hospital, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, China.
Department of Ophthalmology, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
Invest Ophthalmol Vis Sci. 2025 Jan 2;66(1):19. doi: 10.1167/iovs.66.1.19.
This study investigated the impact of hyperglycemia in type 2 diabetes mellitus (T2DM) on the circadian rhythms and function of lacrimal glands (LGs) in contributing to dry eye syndrome. We assessed the effects of hyperglycemia on circadian gene expression, immune cell recruitment, neural activity, and metabolic pathways, and evaluated the effectiveness of insulin in restoring normal LG function.
Using a T2DM mouse model (db/db mice), circadian transcriptomic changes in LGs were analyzed through RNA sequencing over a 24-hour period. Rhythmic expression of core clock genes, immune and neural activity, and metabolic pathways were evaluated. The effects of insulin treatment on these parameters were also assessed.
Hyperglycemia disrupted the circadian expression of core clock genes in LGs, leading to a 50% reduction in rhythmic gene expression. This was associated with altered immune cell recruitment, impaired neural activity, and metabolic changes. Insulin treatment lowered blood glucose levels but did not restore normal circadian function or tear secretion, exacerbating dry eye syndrome in diabetic mice.
T2DM significantly disrupts circadian rhythms and function in lacrimal glands, contributing to dry eye syndrome. The limited efficacy of insulin in restoring circadian regulation suggests that hyperglycemia-induced dysfunction in LGs is not solely dependent on blood glucose levels, highlighting the need for therapies targeting circadian rhythms in diabetic ocular complications.
本研究调查2型糖尿病（T2DM）中的高血糖对泪腺昼夜节律和功能的影响，泪腺昼夜节律和功能与干眼症相关。我们评估了高血糖对昼夜节律基因表达、免疫细胞募集、神经活动和代谢途径的影响，并评估了胰岛素恢复泪腺正常功能的有效性。
使用T2DM小鼠模型（db/db小鼠），通过RNA测序在24小时内分析泪腺的昼夜转录组变化。评估核心生物钟基因的节律性表达、免疫和神经活动以及代谢途径。还评估了胰岛素治疗对这些参数的影响。
高血糖破坏了泪腺中核心生物钟基因的昼夜表达，导致节律性基因表达降低50%。这与免疫细胞募集改变、神经活动受损和代谢变化有关。胰岛素治疗降低了血糖水平，但未恢复正常的昼夜功能或泪液分泌，加重了糖尿病小鼠的干眼症。
T2DM显著破坏泪腺的昼夜节律和功能，导致干眼症。胰岛素在恢复昼夜节律调节方面的疗效有限，表明高血糖诱导的泪腺功能障碍并非仅依赖于血糖水平，这突出了针对糖尿病眼部并发症的昼夜节律进行治疗的必要性。
