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Glucagon-like peptide-1 receptor expression in the human eye.


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.

SUBMITTER: Hebsgaard JB 

PROVIDER: S-EPMC6099507 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Glucagon-like peptide-1 receptor expression in the human eye.

Hebsgaard Josephine B JB   Pyke Charles C   Yildirim Emre E   Knudsen Lotte B LB   Heegaard Steffen S   Kvist Peter H PH  

Diabetes, obesity & metabolism 20180524 9


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 a  ...[more]

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