A gatekeeper sympathetic control of lacrimal tear secretion and dry eye onset through the NA-Adra1a-Ucp2 pathway

Mingli Qu, Qun Wang, Xiaofei Bai, Jing Feng, Sai Zhang, Yangyang Zhang, Qing Chen, Hai Zhu, Hengrui Zhang, Qunqin Guo, Bin Zhang, Shengqian Dou, Yujie Qiao, Hongwei Wang, Yihai Cao, Lixin Xie () and Qingjun Zhou ()
Additional contact information
Mingli Qu: Eye Institute of Shandong First Medical University
Qun Wang: Eye Institute of Shandong First Medical University
Xiaofei Bai: Eye Institute of Shandong First Medical University
Jing Feng: Eye Institute of Shandong First Medical University
Sai Zhang: Eye Institute of Shandong First Medical University
Yangyang Zhang: Eye Institute of Shandong First Medical University
Qing Chen: Shandong Second Medical University
Hai Zhu: University of Health and Rehabilitation Sciences
Hengrui Zhang: Eye Institute of Shandong First Medical University
Qunqin Guo: Eye Institute of Shandong First Medical University
Bin Zhang: Eye Institute of Shandong First Medical University
Shengqian Dou: Eye Institute of Shandong First Medical University
Yujie Qiao: Eye Institute of Shandong First Medical University
Hongwei Wang: Eye Institute of Shandong First Medical University
Yihai Cao: Karolinska Institute
Lixin Xie: Eye Institute of Shandong First Medical University
Qingjun Zhou: Eye Institute of Shandong First Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Tear secretion from the lacrimal gland is essential for maintaining ocular surface homeostasis, and its insufficiency causes aqueous-deficient dry eye. Unlike the well-established parasympathetic neuronal regulation, the role of sympathetic nervous system (SNS) in tear secretion remains controversial. Here, we demonstrate the intact sympathetic innervation in lacrimal gland and its activation under multiple dry eye stresses. Pharmacological, surgical, and genetic blockade of SNS increases tear secretion and alleviates dry eye signs. Mechanistically, SNS-driven noradrenaline (NA) release activates α1a-adrenergic receptor (Adra1a) in acinar and myoepithelial cells to regulate mitochondrial Ucp2 and tear secretion. Systemic and local delivery of Adra1a antagonists, including silodosin and tamsulosin, improves tear secretion and reduces corneal lesions in multiple dry eye mouse models. In addition, we identify the brain locus coeruleus as an upstream driver orchestrating sympathetic regulation of lacrimal secretion. Overall, these findings reveal a gatekeeper role of SNS in tear secretion and offer potential therapeutic strategies for dry eye disease.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-60476-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60476-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-60476-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().