Background: Increasing attention has been attracted by the role of circular RNAs 
(circRNAs) in ocular diseases. Previous study has revealed that circ_0005941 
(also known as circFTO, an alpha-ketoglutarate-dependent dioxygenase) was 
upregulated in the vitreous humor of diabetic retinopathy (DR), while its 
underlying mechanism in DR remains unknown. Methods: Retinal vascular 
endothelial cells (RVECs) treated with high glucose (HG) were used to establish 
the DR cell model. The in vivo assays were conducted using 
streptozotocin-induced diabetic mice. The circular structure and stability of 
circFTO were identified by Sanger sequencing and RNase R treatment. RT-qPCR 
analysis was used to detect the RNA expression. The levels of the mRNA-encoded 
protein thioredoxin-interacting protein (TXNIP) or angiogenesis-associated 
proteins (VEGFA, PDGF, and ANG2) and blood-retinal barrier (BRB)-related 
proteins (ZO-1, Occludin, and Claudin-5) were measured by Western blot. The 
viability of RVECs was measured using CCK-8 assays. The angiogenesis of RVECs 
was assessed using tube formation assays in vitro. Endothelial permeability 
assays were conducted to examine the function of the BRB. The binding between 
genes was explored using RNA pulldown and luciferase reporter assays. Results: 
CircFTO was upregulated in HG-treated RVECs. CircFTO deficiency reversed the 
HG-induced increase in the viability and angiogenesis of RVECs and alleviated 
HG-mediated impairment of the BRB. MiR-128-3p bound with circFTO and was 
downregulated in HG-treated RVECs. TXNIP was a downstream target gene of 
miR-128-3p. TXNIP was highly expressed in the DR cell model. Rescue assays 
revealed that circFTO promoted angiogenesis and impaired the blood-retinal 
barrier by upregulating TXNIP. In the DR mouse model, circFTO silencing 
inhibited angiogenesis and promoted BRB recovery in vivo. Conclusion: CircFTO 
promotes angiogenesis and impairs the blood-retinal barrier in vitro and in vivo 
by binding with miR-128-3p to upregulate TXNIP in DR.