Ursodeoxycholic acid ameliorates diabetic retinopathy via reducing retinal inflammation and reversing the breakdown of blood-retinal barrier.

Ursodeoxycholic acid (UDCA) is the hydrolysis of tauroursodeoxycholic acid, which is the main ingredient from bear gall that has functions including clearing heat and detoxification, and improving eyesight. However, whether UDCA has improving effects on diabetic retinopathy (DR) is not known. This study aims to observe the amelioration of UDCA on DR and its engaged mechanisms. The results of Evans blue permeation assay showed that UDCA (15, 30 mg/kg) reversed the breakdown of blood-retinal barrier (BRB) and the decreased expression of claudin-1 and claudin-19 in STZ-induced diabetic mice. UDCA reversed the reduced thickness of both inner nuclear layer (INL) and outer nuclear layer (ONL) in STZ-induced diabetic mice. UDCA reduced retinal ionized calcium-binding adapter molecule 1 (Iba1) expression in STZ-induced diabetic mice. UDCA reduced the expression of phosphorylated the inhibitor of nuclear factor κB kinase (IKK) and the nuclear translocation of p65 subunit of nuclear factor κB (NFκB) in retinas from STZ-induced diabetic mice. UDCA also reduced retinal expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), intercellular cell adhesion molecule-1 (ICAM-1), inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) in STZ-induced diabetic mice. In conclusion, UDCA attenuates BRB breakdown during DR development via inhibiting retinal inflammation and reversing the reduced expression of tight junctions (TJs) including claudin-1 and claudin-19.