Topical Administration of GLP-1 Receptor Agonists Prevents Retinal Neurodegeneration in Experimental Diabetes
| Autor: | Ángela M. Valverde, Marta García-Ramírez, José A. Arranz, Lidia Corraliza, Rafael Simó, Ana I. Arroba, Cristina Hernández, Cristina Solà-Adell, Patricia Bogdanov |
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| Rok vydání: | 2015 |
| Předmět: |
Agonist
Male endocrine system medicine.medical_specialty medicine.drug_class Endocrinology Diabetes and Metabolism Blotting Western Administration Ophthalmic Apoptosis Biology Real-Time Polymerase Chain Reaction Neuroprotection Glucagon-Like Peptide-1 Receptor Retina Diabetes Mellitus Experimental chemistry.chemical_compound Mice Glucagon-Like Peptide 1 Internal medicine Glial Fibrillary Acidic Protein Internal Medicine medicine Electroretinography Animals Humans Glucagon-like peptide 1 receptor Aged Diabetic Retinopathy Liraglutide Venoms digestive oral and skin physiology Neurodegeneration Retinal Middle Aged medicine.disease Immunohistochemistry medicine.anatomical_structure Endocrinology Neuroprotective Agents chemistry Diabetes Mellitus Type 2 Systemic administration Exenatide Female Peptides medicine.drug Retinal Neurons |
| Zdroj: | Diabetes. 65(1) |
| ISSN: | 1939-327X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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