miR-20a-5p alleviates diabetic retinopathy by targeting TXNIP to inhibit NLRP3 inflammasome-dependent pyroptosis.

OBJECTIVE

This study aimed to investigate whether microRNA-20a-5p (miR-20a-5p) plays a protective role in diabetic retinopathy (DR) by regulating NLRP3/caspase-1-mediated pyroptosis through targeting thioredoxin-interacting protein (TXNIP).

METHODS

Serum samples from patients with DR and healthy volunteers were collected to determine miR-20a-5p expression. In vitro, rat retinal Müller cells (RMC-1) were treated with high glucose (45 mM) to analyze changes in cell viability, oxidative stress, pyroptosis, and key molecules in the NLRP3 pathway. In vivo, a diabetic rat model was induced by streptozotocin. Intravitreal injection of lentivirus was used to modulate retinal miR-20a-5p and TXNIP expression, and the effects on blood glucose, body weight, retinal histopathology, and pyroptosis-related proteins were assessed.

RESULTS

Serum miR-20a-5p expression was significantly downregulated in patients with DR. In vitro experiments demonstrated that high glucose decreased miR-20a-5p expression and increased TXNIP expression in RMC-1 cells, activated the NLRP3/caspase-1 pathway, and induced pyroptosis and the release of inflammatory factors (IL-1β and IL-18). Overexpression of miR-20a-5p directly targeted and inhibited TXNIP, thereby suppressing NLRP3 inflammasome activation and alleviating oxidative stress and pyroptosis. This protective effect was reversed by TXNIP overexpression or an NLRP3 activator (nigericin). In vivo experiments showed that intravitreal overexpression of miR-20a-5p improved metabolic parameters, alleviated retinal tissue damage, and inhibited pyroptosis pathway protein expression in diabetic rats. Co-overexpression of TXNIP offset these protective effects.

CONCLUSION

miR-20a-5p is downregulated in DR. By targeting and negatively regulating TXNIP, it inhibits overactivation of the downstream NLRP3/caspase-1 signaling pathway, thereby mitigating retinal cell pyroptosis and inflammatory responses as one of the protective mechanisms in DR.