Evidence mapPaperPMID 40473608Full record

ArticleNature communications2025

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 and 7 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Mingli Qu *Eye Institute of Shandong First Medical University, Qingdao, Shandong, China.
Qun Wang *Eye Institute of Shandong First Medical University, Qingdao, Shandong, China.
Xiaofei BaiEye Institute of Shandong First Medical University, Qingdao, Shandong, China.
Jing FengEye Institute of Shandong First Medical University, Qingdao, Shandong, China.ORCID http://orcid.org/0000-0003-3719-9319
Sai ZhangEye Institute of Shandong First Medical University, Qingdao, Shandong, China.
Yangyang ZhangEye Institute of Shandong First Medical University, Qingdao, Shandong, China.
Qing ChenSchool of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China.
Hai ZhuDepartment of Urology, Qingdao Hospital, University of Health and Rehabilitation Sciences, Qingdao, Shandong, China.
Hengrui ZhangEye Institute of Shandong First Medical University, Qingdao, Shandong, China.
Qunqin GuoEye Institute of Shandong First Medical University, Qingdao, Shandong, China.
Bin ZhangEye Institute of Shandong First Medical University, Qingdao, Shandong, China.
Shengqian DouEye Institute of Shandong First Medical University, Qingdao, Shandong, China.
Yujie QiaoEye Institute of Shandong First Medical University, Qingdao, Shandong, China.
Hongwei WangEye Institute of Shandong First Medical University, Qingdao, Shandong, China.
Yihai CaoDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, Solna, Sweden.ORCID http://orcid.org/0000-0003-1308-0065
Lixin XieEye Institute of Shandong First Medical University, Qingdao, Shandong, China. lixin_xie@hotmail.com.
Qingjun ZhouEye Institute of Shandong First Medical University, Qingdao, Shandong, China. qjzhou2000@hotmail.com.ORCID http://orcid.org/0000-0002-7770-9275

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Dry Eye SyndromesLacrimal ApparatusNorepinephrineReceptors, Adrenergic, alpha-1Sympathetic Nervous SystemTearsUncoupling Protein 2Adrenergic alpha-1 Receptor AntagonistsAnimalsDisease Models, AnimalFemaleHumansMaleMiceMice, Inbred C57BLSignal TransductionAdrenergic alpha-1 Receptor AntagonistsNorepinephrineReceptors, Adrenergic, alpha-1Uncoupling Protein 2

Identifiers

PMID40473608
PMCPMC12141490

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.