tRNA-derived fragment tRF-30 propels diabetes-induced retinal microvascular complications by regulating STAT3 signaling.

Transfer RNA-derived fragments (tRFs) represent a novel class of non-coding RNA transcripts that possess specific biological functions. However, the involvement of tRFs in retinal microvascular diseases remains poorly understood. In this study, we aimed to reveal whether modulation of tRF-30 expression could attenuate pathological retinal neovascular diseases. Our findings demonstrate a significant upregulation of tRF-30 expression levels in both in vivo models of diabetic retinopathy (DR) and in vitro endothelial sprouting models. Conversely, inhibition of tRF-30 expression suppressed the formation of abnormal neovascularization in the retina in vivo, while reducing the proliferation and migration activity of retinal vascular endothelial cells in vitro. We also found that tRF-30 modulates retinal neovascularization through the tRF-30/TRIB3/signal transducer and activated transcription 3 signaling pathway. Furthermore, we validated a significant upregulation of tRF-30 expression levels in the vitreous humor of DR patients, with high levels of both validity and specificity in diagnostic testing. Collectively, our findings highlight a pro-angiogenic role for tRF-30 in DR. Intervening in the tRF-30 signaling pathway may represent a promising prevention and treatment strategy for retinal angiogenesis.

tRNA-derived fragment tRF-1020 ameliorates diabetes-induced retinal microvascular complications.

Transfer RNA (tRNA)-derived fragments are the non-coding single-stranded RNAs involved in several physiological and pathological processes. Herein, we investigated the role of tRF-1020, a tRNA fragment, in diabetes-induced retinal microvascular complications. The results showed that the levels of tRF-1020 expression were down-regulated in diabetic retinal vessels and retinal endothelial cells following high glucose or H2 O2 stress. Overexpressing tRF-1020 led to decreased endothelial cell viability, proliferation, migration, and tube formation and alleviated retinal vascular dysfunction as shown by decreased retinal acellular capillaries, vascular leakage, and inflammation. By contrast, tRF-1020 silencing displayed the opposite effects. tRF-1020 regulated endothelial angiogenic functions and retinal vascular dysfunction by targeting Wnt signalling. Moreover, the levels of tRF-1020 expression were reduced in aqueous humour and vitreous samples of the patients with diabetic retinopathy. Collectively, tRF-1020 is a potential target for the diagnosis and treatment of diabetic retinopathy.