Abstract
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.
| Original language | English |
|---|---|
| Journal | Diabetes, Obesity and Metabolism |
| Volume | 20 |
| Issue number | 9 |
| Pages (from-to) | 2304-2308 |
| Number of pages | 5 |
| ISSN | 1462-8902 |
| DOIs | |
| Publication status | Published - Sept 2018 |
Keywords
- Adult
- Aged
- Diabetes Mellitus, Type 2/complications
- Diabetic Retinopathy/etiology
- Eye/metabolism
- Female
- Glucagon-Like Peptide-1 Receptor/metabolism
- Humans
- Immunohistochemistry
- In Situ Hybridization
- Male
- Middle Aged
- RNA, Messenger/metabolism
