Liraglutide preserves endothelial function in ophthalmic arteries of septic mice via prevention of oxidative stress.

We hypothesized that the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide enhances endothelial functions in ophthalmic arteries of mice with polymicrobial sepsis. The study involved three groups of mice. Two groups underwent cecal ligation and puncture (CLP) to induce polymicrobial sepsis, with one of these groups receiving liraglutide treatment. The third group underwent sham surgery as a control. 24 h after the CLP procedure, the mice were euthanized, and ophthalmic arteries were isolated either for in vitro analysis of vascular function using videomicroscopy or for quantification of reactive oxygen species and redox genes or enzymes by PCR or immunohistochemistry. Vasoconstriction responses to the α-adrenoceptor agonist phenylephrine and vasodilation responses to sodium nitroprusside, an endothelium-independent vasodilator, were similar across all three groups. However, responses to acetylcholine, an endothelium-dependent vasodilator, were significantly impaired in ophthalmic arteries of septic mice. Notably, acetylcholine responses were preserved in septic mice treated with liraglutide. Additionally, dihydroethidium, and NOX2 antibody staining revealed a significant increase in markers for oxidative stress in the ophthalmic arteries of endotoxaemic mice, but not in those treated with liraglutide. In conclusion, activation of the GLP-1 receptor by liraglutide restrains endothelial dysfunction, reduces oxidative stress, and inhibits NOX2 overexpression in the ophthalmic arteries of endotoxaemic mice. These data suggest that GLP-1 receptor activation may provide a promising therapeutic strategy for treating ocular diseases characterized by oxidative stress and endothelial dysfunction.