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High glucose induces pyroptosis of retinal microglia through NLPR3 inflammasome signaling
Libin Huang1, Junmei You1, Yao Yao1
1The First Affiliated Hospital of Fujian Medical University, China.
Purpose:
Diabetic retinopathy is currently considered a chronic inflammatory disease involving NOD-like receptor family pyrin domain containing 3 inflammasome activation and retinal microglial pyroptosis. In this study, we aimed to investigate whether NOD-like receptor family pyrin domain containing 3 inflammasome signaling induces pyroptotic death of retinal microglia under high-glucose conditions.
Methods:
Retinal microglia were stimulated by high glucose levels for 24 h. Cell viability, lactate dehydrogenase release, and caspase-1 activity were detected in vitro. The expression of pro-inflammatory cytokine (interleukin-1β, activated microglia marker ionized calcium-binding adapter molecule-1), NOD-like receptor family pyrin domain containing 3, cleaved caspase-1, and cleaved gasdermin D were examined. Subsequently, retinal microglia were pretreated with the inhibitors of NOD-like receptor family pyrin domain containing 3 inflammasome signaling prior to stimulation with high glucose, and their molecular and functional changes were evaluated.
Results:
High-glucose (25, 50, or 100 mM) stimulation decreased cell viability, but enhanced lactate dehydrogenase release and caspase-1 activity in a dose-dependent manner. Moreover, high glucose upregulated the protein expression of interleukin-1β, ionized calcium-binding adapter molecule-1, NOD-like receptor family pyrin domain containing 3, cleaved caspase-1, and cleaved gasdermin D. However, pretreatment with the inhibitors of NOD-like receptor family pyrin domain containing 3 inflammasome signaling inhibited high glucose (25 mM)-induced cytotoxicity, NOD-like receptor family pyrin domain containing 3 inflammasome activation, and pyroptosis of retinal microglia.
Conclusions:
NOD-like receptor family pyrin domain containing 3 inflammasome signaling may modulate retinal microglia-related inflammation and pyroptosis under high-glucose conditions.
Insights
High glucose triggers inflammation and cell death in retinal microglia via NOD-like receptor family pyrin domain containing 3 inflammasome activation. Inhibiting this pathway protects against diabetic retinopathy-related damage.
Area of Science:
- Ophthalmology
- Immunology
- Cell Biology
Background:
- Diabetic retinopathy is a chronic inflammatory condition.
- Retinal microglial activation and pyroptosis are key pathological features.
- NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation is implicated in this process.
Purpose of the Study:
- To investigate if NLRP3 inflammasome signaling drives pyroptotic death of retinal microglia under high-glucose conditions.
- To explore the role of NLRP3 inflammasome in diabetic retinopathy pathogenesis.
Main Methods:
- Retinal microglia were exposed to high glucose concentrations in vitro.
- Assessed cell viability, lactate dehydrogenase release, and caspase-1 activity.
- Examined protein expression of inflammatory markers, NLRP3, caspase-1, and gasdermin D.
- Evaluated the effects of NLRP3 inflammasome inhibitors on high glucose-induced changes.
Main Results:
- High glucose dose-dependently reduced cell viability and increased inflammatory markers.
- Upregulated protein expression of IL-1β, Iba1, NLRP3, cleaved caspase-1, and cleaved gasdermin D.
- NLRP3 inflammasome inhibition mitigated high glucose-induced cytotoxicity and pyroptosis.
Conclusions:
- NLRP3 inflammasome signaling plays a crucial role in high glucose-induced retinal microglia inflammation and pyroptosis.
- Targeting NLRP3 inflammasome may offer a therapeutic strategy for diabetic retinopathy.
