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Topical Administration of GLP-1 Receptor Agonists Prevents Retinal Neurodegeneration in Experimental Diabetes.
Diabetes. 2016 Jan; 65(1):172-87.D

Abstract

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.

Authors+Show Affiliations

Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain CIBERDEM, Instituto de Salud Carlos III, Madrid, Spain cristina.hernandez@vhir.org.Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain CIBERDEM, Instituto de Salud Carlos III, Madrid, Spain.Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain CIBERDEM, Instituto de Salud Carlos III, Madrid, Spain.Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain CIBERDEM, Instituto de Salud Carlos III, Madrid, Spain.Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain CIBERDEM, Instituto de Salud Carlos III, Madrid, Spain.Unidad de Metabolopatías, Laboratorios Clínicos, Hospital Universitari Vall d'Hebron, Barcelona, Spain.CIBERDEM, Instituto de Salud Carlos III, Madrid, Spain Instituto de Investigaciones Biomédicas "Alberto Sols," Consejo Superior de Investigaciones Científicas/Universidad Autónoma de Madrid, Madrid, Spain.CIBERDEM, Instituto de Salud Carlos III, Madrid, Spain Instituto de Investigaciones Biomédicas "Alberto Sols," Consejo Superior de Investigaciones Científicas/Universidad Autónoma de Madrid, Madrid, Spain.Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain CIBERDEM, Instituto de Salud Carlos III, Madrid, Spain.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26384381

Citation

Hernández, Cristina, et al. "Topical Administration of GLP-1 Receptor Agonists Prevents Retinal Neurodegeneration in Experimental Diabetes." Diabetes, vol. 65, no. 1, 2016, pp. 172-87.
Hernández C, Bogdanov P, Corraliza L, et al. Topical Administration of GLP-1 Receptor Agonists Prevents Retinal Neurodegeneration in Experimental Diabetes. Diabetes. 2016;65(1):172-87.
Hernández, C., Bogdanov, P., Corraliza, L., García-Ramírez, M., Solà-Adell, C., Arranz, J. A., Arroba, A. I., Valverde, A. M., & Simó, R. (2016). Topical Administration of GLP-1 Receptor Agonists Prevents Retinal Neurodegeneration in Experimental Diabetes. Diabetes, 65(1), 172-87. https://doi.org/10.2337/db15-0443
Hernández C, et al. Topical Administration of GLP-1 Receptor Agonists Prevents Retinal Neurodegeneration in Experimental Diabetes. Diabetes. 2016;65(1):172-87. PubMed PMID: 26384381.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Topical Administration of GLP-1 Receptor Agonists Prevents Retinal Neurodegeneration in Experimental Diabetes. 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, Y1 - 2015/09/17/ PY - 2015/03/31/received PY - 2015/09/08/accepted PY - 2015/9/19/entrez PY - 2015/9/19/pubmed PY - 2016/4/29/medline SP - 172 EP - 87 JF - Diabetes JO - Diabetes VL - 65 IS - 1 N2 - 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. SN - 1939-327X UR - https://www.unboundmedicine.com/medline/citation/26384381/Topical_Administration_of_GLP_1_Receptor_Agonists_Prevents_Retinal_Neurodegeneration_in_Experimental_Diabetes_ L2 - http://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=26384381 DB - PRIME DP - Unbound Medicine ER -