Glucagon‐like peptide‐1 receptor expression in the human eye

Semaglutide is a human glucagon‐like peptide‐1 (GLP‐1) analogue that is in development for the treatment of type 2 diabetes. In the pre‐approval cardiovascular outcomes trial SUSTAIN 6, semaglutide was associated with a significant increase in the risk of diabetic retinopathy (DR) complications vs placebo. GLP‐1 receptor (GLP‐1R) expression has previously been demonstrated in the retina in animals and humans; however, antibodies used to detect expression have been documented to be non‐specific and fail to detect the GLP‐1R using immunohistochemistry (IHC), a problem common for many G‐protein coupled receptors. Using a validated GLP‐1R antibody for IHC and in situ hybridization for GLP‐1R mRNA in normal human eyes, GLP‐1Rs were detected in a small fraction of neurons in the ganglion cell layer. In advanced stages of DR, GLP‐1R expression was not detected at the protein or mRNA level. Specifically, no GLP‐1R expression was found in the eyes of people with long‐standing proliferative DR (PDR). In conclusion, GLP‐1R expression is low in normal human eyes and was not detected in eyes exhibiting advanced stages of PDR.