Abstract
Purpose :
Glucagon-like peptide-1 (GLP-1) receptor agonists can improve glycemic control in diabetic patients, but evidence suggests that the GLP-1 receptor agonist semaglutide can increase the risk of developing diabetic retinopathy (DR). DR is characterized by disturbances in flow regulation that involve both smaller and larger resistance vessels, and the regulation of flow involves the effect of nitric oxide (NO). Therefore, the purpose of the present study was to examine the vasoactive effects of the GLP-1 receptor agonists semaglutide and liraglutide on retinal resistance vessels at different branching level.
Methods :
Porcine superior hemiretinas (n=26) were mounted in a specially designed perfusion chamber, and the diameter of retinal arterioles, pre-capillary arterioles and capillaries were studied before and during intravascular administration of liraglutide and semaglutide, each in concentrations of 10-10, 10-7 and 10-4 M. The experiments were repeated in the presence of the non-selective NO synthase inhibitor L-NAME.
Results :
Intravascular administration of liraglutide and semaglutide induced significant constriction of arterioles but significant dilatation of pre-capillary arterioles and capillaries at all three concentrations (p<0.01 for all comparisons). The constriction of arterioles by both compounds was inhibited by L-NAME (p≤0.02 for both comparisons) whereas the dilatation of pre-capillary arterioles and capillaries induced by semaglutide was enhanced by L-NAME (p<0.01 for all comparisons).
Conclusions :
The vasoactive effects of liraglutide and semaglutide are opposite among larger and smaller retinal resistance vessels. This may contribute to the pattern of effects and adverse effects of GLP-1 agonists on the retina in vivo.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.