<b>Targeting tsRNA-1797 alleviates diabetes-induced vascular dysfunction through modulating purine metabolism</b>

<p dir="ltr"><a href="" target="_blank">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.</a> 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 <i>in vitro</i>, and inhibited retinal vascular dysfunction <i>in vivo</i>. 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.</p>