Figure 1.

Liver X receptor perturbations of lipid metabolism in diabetic retinopathy. Under normal physiological conditions, transcriptional activity of LXRs is increased in response to elevated cellular levels of cholesterol. A high glucose environment attenuates activation of LXR, inducing the downregulations of transporters ABCA1 and ABCG1 on the cell membrane. Consequence of cellular cholesterol accumulation causes oxidative stress and inflammation in vascular endothelial cells. Furthermore, the increased expression level of VEGF downregulates tight junction proteins ZO-1 and occludin, leading to blood-retinal breakdown. LXR agonists can eventually reverse this pathological process. LXR: liver X receptor; RXR: retinoid X receptor; ABCA1: ATP-binding cassette subfamily A member 1; ABCG1: ATP-binding cassette subfamily G member 1; apo: apolipoprotein; ZO-1: zonula occludens-1.