2015/09/17 by Cristina Hernández, Patricia Bogdanov, Lidia Corraliza +10 · 260 citations
Biochemistry, Genetics and Molecular Biology · Medicine · Neuroscience · #Adenosine and Purinergic Signaling #Agonist #Biology #Diabetes Treatment and Management #Diabetes mellitus #Diabetic retinopathy #Endocrinology #Exenatide #Internal medicine #Liraglutide #Medicine #Neurodegeneration #Neuroprotection #Neuroscience #Ophthalmology #Pharmacology #Receptor #Retina #Retinal #Retinal Diseases and Treatments #Systemic administration #Type 2 diabetes
paper · pdf · doi:10.2337/db15-0443
published in Diabetes 65(1), 172-187 (American Diabetes Association)
openalex publication_date 2015/09/17 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/05
Retinal neurodegeneration is an early event in the pathogenesis of diabetic retinopathy (DR). Since glucagon-like peptide 1 (GLP-1) exerts neuroprotective effects in the central nervous system and the retina is ontogenically a brain-derived tissue, the aims of the current study were as follows: 1) to examine the expression and content of GLP-1 receptor (GLP-1R) in human and db/db mice retinas; 2) to determine the retinal neuroprotective effects of systemic and topical administration (eye drops) of GLP-1R agonists in db/db mice; and 3) to examine the underlying neuroprotective mechanisms. We have found abundant expression of GLP-1R in the human retina and retinas from db/db mice. Moreover, we have demonstrated that systemic administration of a GLP-1R agonist (liraglutide) prevents retinal neurodegeneration (glial activation, neural apoptosis, and electroretinographical abnormalities). This effect can be attributed to a significant reduction of extracellular glutamate and an increase of prosurvival signaling pathways. We have found a similar neuroprotective effect using topical administration of native GLP-1 and several GLP-1R agonists (liraglutide, lixisenatide, and exenatide). Notably, this neuroprotective action was observed without any reduction in blood glucose levels. These results suggest that GLP-1R activation itself prevents retinal neurodegeneration. Our results should open up a new approach in the treatment of the early stages of DR.