Evidence mapPaperPMID 41588940Full record

ArticleEndocrinology, diabetes & metabolism2026

Targeting the NEK7/NLRP3 Inflammasome Axis: Synergistic Protection of Intravitreal MCC950 and Systemic Metformin Against Diabetic Retinopathy in Rats.

Kexuan Ren, Xiaofeng Li

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Article in Endocrinology, diabetes & metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

2 authors.

Kexuan RenDalian University Affiliated Xinhua Hospital, Dalian, liaoning, China.ORCID https://orcid.org/0000-0002-1352-1759
Xiaofeng LiDalian University Affiliated Xinhua Hospital, Dalian, liaoning, China.ORCID https://orcid.org/0000-0003-2060-8155

Funding

China Medicine Education Association Project 2024KTM031
6 · The paper itself

Abstract

objectiveDiabetic retinopathy (DR) is characterised by chronic neuroinflammation where the NLRP3 inflammasome plays a pivotal role. This study investigated the therapeutic potential and underlying mechanism of combining systemic metformin (MET) with intravitreal MCC950, a specific NLRP3 inhibitor, in a rodent model of DR.

methodsA type 2 diabetic rat model was induced by high-fat diet and streptozotocin (STZ) injection. Diabetic rats were divided into DR, MET, MCC950 and MET+MCC950 treatment groups. Body weight and blood glucose were monitored. Retinal structural changes were assessed by HE and PAS staining. Apoptosis was detected by TUNEL assay, and oxidative stress was evaluated by ROS fluorescence. The expression and interaction of key proteins within the NEK7/NLRP3 pathway were analysed by Western blot and immunofluorescence.

resultsThe DR group exhibited significant retinal thinning, increased acellular capillaries, elevated apoptosis and oxidative stress. While monotherapies showed partial improvement, the MET+MCC950 combination yielded the most robust protective effects, nearly restoring retinal morphology and significantly reducing apoptosis and ROS levels. Mechanistically, combination therapy most effectively suppressed the activation of the NEK7/NLRP3 inflammasome pathway, as evidenced by decreased protein levels of NEK7, NLRP3, ASC, cleaved-Caspase-1 and IL-1β. Immunofluorescence confirmed enhanced NEK7/NLRP3 interaction in DR, which was markedly inhibited by the combination treatment. A significant positive correlation was found between ROS levels and NEK7 expression.

conclusionThe study demonstrates that the combination of systemic metformin and intravitreal MCC950 confers superior protection against DR by synergistically inhibiting the NEK7/NLRP3 inflammasome pathway, resulting in reduced oxidative stress, apoptosis and inflammatory response. This novel combinational strategy presents a promising therapeutic approach for DR.

Indexed as

Diabetic RetinopathyFuransHeterocyclic Compounds, 4 or More RingsHypoglycemic AgentsIndenesInflammasomesMetforminNIMA-Related KinasesNLR Family, Pyrin Domain-Containing 3 ProteinSulfonamidesSulfonesAnimalsApoptosisDiabetes Mellitus, ExperimentalDrug SynergismIntravitreal InjectionsFuransHeterocyclic Compounds, 4 or More RingsHypoglycemic AgentsIndenesInflammasomesMetforminN-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamideNIMA-Related KinasesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, ratSulfonamidesSulfonesapoptosisdiabetic retinopathyMCC950metforminNEK7NLRP3 inflammasomeoxidative stresssynergistic therapy

Identifiers

PMID41588940
PMCPMC12835612

What Socratic holds

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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.