Glucagon‐like peptide‐1 receptor expression in the human eye
Open accessAbstract
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.
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GLP-1 acts through GLP-1R, which is mainly expressed in pancreatic islets, the brain, and the GI tract, and less prominently in the kidney and eyes.
“GLP-1 acts through a class 2 member of the G-coupled protein C receptor family seven-transmembrane receptor (GLP-1R) (8), which is mainly expressed in pancreatic islets, the brain, and the gastrointestinal (GI) tract (9–12), and less prominently in the kidney and eyes (11–13).”
From The science of safety: adverse effects of GLP-1 receptor agonists as glucose-lowering and obesity medications (2026) · cites this paper as [13]
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“GLP-1 acts through a class 2 member of the G-coupled protein C receptor family seven-transmembrane receptor (GLP-1R) (8), which is mainly expressed in pancreatic islets, the brain, and the gastrointestinal (GI) tract (9–12), and less prominently in the kidney and eyes (11–13).”
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- Authors
- Hebsgaard, J. B., Pyke, C., Yildirim, E., Knudsen, L. B., Heegaard, S., & Kvist, P. H.
- Affiliations
- Novo Nordisk (Denmark) (DK)
- University of Copenhagen (DK)
- Corresponding author
- Knudsen, Lotte B.
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2018-05-24
- Volume
- 20
- Issue
- 9
- Pages
- 2304-2308
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- PMC
- PMC6099507
- OpenAlex
- W2802890213
- Cited by
- 88
- References
- 6
- Citations by year
- 2026: 24 · 2025: 18 · 2024: 16 · 2023: 5 · 2022: 9 · 2021: 5 · 2020: 4 · 2019: 2 · 2018: 5
- FWCI
- 4.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Obesity and Metabolism (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc)
- Funders
- Novo Nordisk A/S
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Keywords
- GLP-1 receptor, semaglutide, diabetic retinopathy, proliferative diabetic retinopathy, retinal ganglion cells, SUSTAIN 6 trial, type 2 diabetes
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Adult, Aged, Diabetes Mellitus, Type 2, Diabetic Retinopathy, Eye, Female, Humans, Immunohistochemistry, Male, Middle Aged, RNA, Messenger, In Situ Hybridization
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