Targeting tsRNA-1797 alleviates diabetes-induced vascular dysfunction through modulating purine metabolism

Diabetes is a metabolic disorder associated with an increased risk of systemic vascular complications. Notably, diabetic retinopathy (DR) represents a major microvascular complication and a leading cause of blindness and vision impairment. Despite its clinical significance, the precise molecular mechanisms underlying vascular dysfunction and the associated metabolic disturbances in DR remain incompletely understood. In this study, we identify tsRNA-1797, a tRNA-derived small RNA, as a critical regulator of retinal vascular dysfunction. tsRNA-1797 expression was markedly up-regulated under diabetic conditions. Functional studies demonstrated that silencing tsRNA-1797 ameliorated endothelial dysfunction in vitro, and inhibited retinal vascular dysfunction in vivo. Mechanistically, tsRNA-1797 was found to disrupt purine metabolism by regulating adenosine production through CD73. The tsRNA-1797-CD73-adenosine axis emerged as a key mediator of retinal vascular dysfunction in DR. These findings establish tsRNA-1797 as a novel regulatory factor that links metabolic dysregulation to vascular dysfunction in DR, highlighting its potential as a promising therapeutic target for diabetic vascular complications.