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

TY - JOUR

T1 - Glucagon-like peptide-1 receptor expression in the human eye

AU - Hebsgaard, Josephine B

AU - Pyke, Charles

AU - Yildirim, Emre

AU - Knudsen, Lotte B

AU - Heegaard, Steffen

AU - Kvist, Peter H

N1 - © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

PY - 2018/9

Y1 - 2018/9

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Diabetes Mellitus, Type 2/complications

KW - Diabetic Retinopathy/etiology

KW - Eye/metabolism

KW - Female

KW - Glucagon-Like Peptide-1 Receptor/metabolism

KW - Humans

KW - Immunohistochemistry

KW - In Situ Hybridization

KW - Male

KW - Middle Aged

KW - RNA, Messenger/metabolism

U2 - 10.1111/dom.13339

DO - 10.1111/dom.13339

M3 - Journal article

C2 - 29707863

SN - 1462-8902

VL - 20

SP - 2304

EP - 2308

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

IS - 9

ER -