ABL1-STAT3-NLRP3 axis attenuates pyroptosis and alleviates diabetic retinopathy

Background Diabetic retinopathy is a major microvascular complication of diabetes and a leading cause of vision loss. Persistent low-grade inflammation drives disease progression. Pyroptosis, characterized by its pro-inflammatory nature, is involved in several inflammatory diseases, yet the molecular mechanisms specific to diabetic retinopathy remain largely undefined. This study aimed to identify the key molecular drivers and regulatory pathways of pyroptosis in diabetic retinopathy. Results Five key pyroptosis-related genes were identified: ubiquitin specific peptidase 24, signal transducer and activator of transcription 3, and ABL proto-oncogene 1 were upregulated, while tripartite motif containing 24 and tubulin beta 6 class VI were downregulated in diabetic retinopathy. High glucose exposure induced pyroptotic morphology and increased lactate dehydrogenase, interleukin-1 beta, and interleukin-18 levels. Functional assays demonstrated that ABL proto-oncogene 1 acts upstream of signal transducer and activator of transcription 3 to activate the NOD-like receptor family pyrin domain containing 3 inflammasome, ultimately leading to pyroptosis. Signal transducer and activator of transcription 3 showed strong diagnostic value with an area under the curve exceeding 0.9. Conclusions This study identifies a novel ABL proto-oncogene 1–signal transducer and activator of transcription 3–NOD-like receptor family pyrin domain containing 3 signaling axis as a central regulator of pyroptosis in diabetic retinopathy. These findings provide insights into inflammation-induced retinal pathology and suggest candidate molecular targets for therapeutic intervention.