Topical Administration of Somatostatin Prevents Retinal Neurodegeneration in Experimental Diabetes
Hernández, Cristina (Hospital Universitari Vall d'Hebron)
Garcia-Ramírez, Marta (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Corraliza Márquez, Lidia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Fernández-Carneado, Jimena (BCN Peptides, Barcelona, Spain)
Farrera-Sinfreu, Josep (BCN Peptides, Barcelona, Spain)
Ponsati, Berta (BCN Peptides, Barcelona, Spain)
González-Rodríguez, Águeda (Instituto de Investigaciones Biomédicas "Alberto Sols")
Valverde, Ángela M. (Instituto de Investigaciones Biomédicas "Alberto Sols")
Simó Canonge, Rafael (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Date:	2013
Abstract:	Retinal neurodegeneration is an early event in the pathogenesis of diabetic retinopathy (DR). Somatostatin (SST) is an endogenous neuroprotective peptide that is downregulated in the diabetic eye. The aim of the study was to test the usefulness of topical administration of SST in preventing retinal neurodegeneration. For this purpose, rats with streptozotocin-induced diabetes mellitus (STZ-DM) were treated with either SST eye drops or vehicle for 15 days. Nondiabetic rats treated with vehicle served as a control group. Functional abnormalities were assessed by electroretinography (ERG), and neurodegeneration was assessed by measuring glial activation and the apoptotic rate. In addition, proapoptotic (FasL, Bid, and activation of caspase-8 and caspase-3) and survival signaling pathways (BclxL) were examined. Intraretinal concentrations of glutamate and its main transporter glutamate/aspartate transporter (GLAST) were also determined. Treatment with SST eye drops prevented ERG abnormalities, glial activation, apoptosis, and the misbalance between proapoptotic and survival signaling detected in STZ-DM rats. In addition, SST eye drops inhibited glutamate accumulation in the retina and GLAST downregulation induced by diabetes mellitus. We conclude that topical administration of SST has a potent effect in preventing retinal neurodegeneration induced by diabetes mellitus. In addition, our findings open up a new preventive pharmacological strategy targeted to early stages of DR.
Grants:	Ministerio de Ciencia e Innovación SAF2012-35562 Ministerio de Ciencia e Innovación SAF2009-08114
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Diabetes, Vol. 62 (june 2013) , p. 2569-2578, ISSN 1939-327X

DOI: 10.2337/db12-0926
PMID: 23474487

10 p, 1.6 MB

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