Single-cell analysis identifies MKI67+ microglia as drivers of neovascularization in proliferative diabetic retinopathy DOI Creative Commons
Kang Zou, Xue Li,

Bibo Ren

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 11, 2025

Proliferative diabetic retinopathy (PDR) is among the primary causes of blindness in individuals with diabetes. Elevated lactate levels have been identified as a critical biomarker associated prognosis PDR. While significant accumulation has observed vitreous fluid PDR patients, detailed pathways through which impacts pathological neovascularization remain insufficiently elucidated. The study employed single-cell RNA sequencing (scRNA-seq) to identify and characterize lactate-associated cell type patients. Key gene expression profiles molecular metabolism were analyzed. In vitro experiments conducted using microglial cultures treated high-glucose conditions (50 mM) assess induction metabolism-related genes. Additionally, an oxygen-induced (OIR) mouse model was used evaluate impact abemaciclib, FDA-approved proliferation inhibitor, on retinal neovascularization. To best our knowledge, this investigation first delineate novel subset, designated MKI67+ microglia, distinguished by robust upregulation genes implicated metabolic processes proliferation, such MKI67, PARK7 LDHA, well pronounced enrichment glycolysis-associated pathways. This unique promotes angiogenesis interacting endothelial cells via secreted phosphoprotein 1 (SPP1)-Integrin alpha 4 (ITGA4) signaling. shown use 50 mM high glucose simulate microglia environment observe its promotion vascular proliferation. vivo OIR model, treatment significantly reduced identification strongly provides perspective mechanisms underlying onset. These findings expand understanding cellular dynamics PDR, emphasizing potential implications for targeted therapeutic interventions.

Language: Английский

Single-cell analysis identifies MKI67+ microglia as drivers of neovascularization in proliferative diabetic retinopathy DOI Creative Commons
Kang Zou, Xue Li,

Bibo Ren

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 11, 2025

Proliferative diabetic retinopathy (PDR) is among the primary causes of blindness in individuals with diabetes. Elevated lactate levels have been identified as a critical biomarker associated prognosis PDR. While significant accumulation has observed vitreous fluid PDR patients, detailed pathways through which impacts pathological neovascularization remain insufficiently elucidated. The study employed single-cell RNA sequencing (scRNA-seq) to identify and characterize lactate-associated cell type patients. Key gene expression profiles molecular metabolism were analyzed. In vitro experiments conducted using microglial cultures treated high-glucose conditions (50 mM) assess induction metabolism-related genes. Additionally, an oxygen-induced (OIR) mouse model was used evaluate impact abemaciclib, FDA-approved proliferation inhibitor, on retinal neovascularization. To best our knowledge, this investigation first delineate novel subset, designated MKI67+ microglia, distinguished by robust upregulation genes implicated metabolic processes proliferation, such MKI67, PARK7 LDHA, well pronounced enrichment glycolysis-associated pathways. This unique promotes angiogenesis interacting endothelial cells via secreted phosphoprotein 1 (SPP1)-Integrin alpha 4 (ITGA4) signaling. shown use 50 mM high glucose simulate microglia environment observe its promotion vascular proliferation. vivo OIR model, treatment significantly reduced identification strongly provides perspective mechanisms underlying onset. These findings expand understanding cellular dynamics PDR, emphasizing potential implications for targeted therapeutic interventions.

Language: Английский

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