Evidence map›Paper›PMID 41361454›Full record

ArticleJournal of neuroinflammation2025

Hyperglycemia impairs microglia responding to retinal vasculopathy via enhanced norepinephrine-ADRB2 signaling.

Shimiao Bu, Bin Mou, Zongqin Xiang, Liting Zhang, Binjie Hao, Junliang Chen, Lang Huang, Xiangcai Ruan, Yong U Liu, Yuehong Zhang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Review
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

10 authors.

Shimiao Bu *Department of Ophthalmology, Laboratory for Neuroimmunology in Health and Disease, Center for Medical Research on Innovation and Translation, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China.
Bin Mou *Department of Ophthalmology, Laboratory for Neuroimmunology in Health and Disease, Center for Medical Research on Innovation and Translation, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China.
Zongqin Xiang *Department of Ophthalmology, Laboratory for Neuroimmunology in Health and Disease, Center for Medical Research on Innovation and Translation, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China.
Liting ZhangDepartment of Ophthalmology, Laboratory for Neuroimmunology in Health and Disease, Center for Medical Research on Innovation and Translation, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China.
Binjie HaoDepartment of Ophthalmology, Laboratory for Neuroimmunology in Health and Disease, Center for Medical Research on Innovation and Translation, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China.
Junliang ChenDepartment of Ophthalmology, Laboratory for Neuroimmunology in Health and Disease, Center for Medical Research on Innovation and Translation, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China.
Lang HuangDepartment of Ophthalmology, Laboratory for Neuroimmunology in Health and Disease, Center for Medical Research on Innovation and Translation, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China.
Xiangcai RuanDepartment of Anesthesia and Pain Medicine, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510655, China.
Yong U LiuDepartment of Ophthalmology, Laboratory for Neuroimmunology in Health and Disease, Center for Medical Research on Innovation and Translation, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China. eyliuy@scut.edu.cn.
Yuehong ZhangDepartment of Ophthalmology, Laboratory for Neuroimmunology in Health and Disease, Center for Medical Research on Innovation and Translation, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China. eyyuehongzhang@scut.edu.cn.

Funding

National Key Research and Development Program of China 2023YFA1800100National Natural Science Foundation of China 82071188Natural Science Foundation of Guangdong Province . 2023A1515010376Natural Science Foundation of Guangzhou Municipality, China 2023A03J0479Science and Technology Projects in Guangzhou 2024A03J1256
6 · The paper itself

Abstract

Breakdown of the blood-retina barrier is a key event in the progression of retinal vascular diseases. Microglia, the resident immune cells of the retina and central nervous system, respond rapidly to vascular injury, yet how hyperglycemia affects this protective function remains unclear. In this study, we combined intravitreal injection of lipopolysaccharide (LPS) with streptozotocin to mimic both acute inflammation under hyperglycemic conditions. LPS triggered a robust increase in microglia-blood vessel interactions (MVIs), mediated by P2Y12 receptor signaling, as confirmed by both pharmacological inhibition and genetic knockout of P2Y12. Live ex vivo retinal imaging demonstrated that microglial processes rapidly converged on injured vessels within 30 min in a P2Y12-dependent manner. However, four weeks of hyperglycemia significantly blunted this MVI response. We found that hyperglycemia elevated circulating norepinephrine (NE), which infiltrated the retina and suppressed MVIs through activation of microglial β2-adrenergic receptors (ADRB2). Ex vivo imaging further showed that pharmacological ADRB2 activation impaired microglial process convergence to sites of vascular injury. Together, these findings reveal that NE-ADRB2 signaling antagonizes P2Y12-mediated microglial engagement with leaky vessels, contributing to BRB breakdown. This study uncovers a novel neuroimmune-vascular mechanism by which hyperglycemia compromises retinal vascular repair and identifies potential therapeutic targets for retinal vascular disorders.

Indexed as

HyperglycemiaMicrogliaNorepinephrineReceptors, Adrenergic, beta-2Retinal DiseasesRetinal VesselsSignal TransductionAnimalsLipopolysaccharidesMaleMiceMice, Inbred C57BLMice, KnockoutReceptors, Purinergic P2Y12RetinaADRB2 protein, mouseLipopolysaccharidesNorepinephrineReceptors, Adrenergic, beta-2Receptors, Purinergic P2Y12ADRB2Blood-retina barrierMicrogliaNorepinephrineRetinal vessel

Identifiers

PMID41361454
PMCPMC12802163

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

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 OpenQuestion graph.