PT  - JOURNAL ARTICLE
AU  - Hernández, Cristina
AU  - Bogdanov, Patricia
AU  - Corraliza, Lidia
AU  - García-Ramírez, Marta
AU  - Solà-Adell, Cristina
AU  - Arranz, José A.
AU  - Arroba, Ana I.
AU  - Valverde, Angela M.
AU  - Simó, Rafael
TI  - Topical Administration of GLP-1 Receptor Agonists Prevents Retinal Neurodegeneration in Experimental Diabetes
AID  - 10.2337/db15-0443
DP  - 2016 Jan 01
TA  - Diabetes
PG  - 172--187
VI  - 65
IP  - 1
4099  - http://diabetes.diabetesjournals.org/content/65/1/172.short
4100  - http://diabetes.diabetesjournals.org/content/65/1/172.full
SO  - Diabetes2016 Jan 01; 65
AB  - 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.