Topical administration of GLP-1 receptor agonists prevents retinal neurodegeneration in experimental diabetes

Cristina Hernández, Patricia Bogdanov, Lidia Corraliza, Marta García-Ramírez, Cristina Solà-Adell, José A. Arranz, Ana I. Arroba, Angela M. Valverde, Rafael Simó

Research output: Contribution to journalArticleResearchpeer-review

82 Citations (Scopus)

Abstract

© 2016 by the American Diabetes Association. Retinal neurodegeneration is an early event in the pathogenesis of diabetic retinopathy (DR). Since glucagonlike 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.
Original languageEnglish
Pages (from-to)172-187
JournalDiabetes
Volume65
Issue number1
DOIs
Publication statusPublished - 1 Jan 2016

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