title: Topical administration of somatostatin prevents retinal neurodegeneration in experimental diabetes.
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.
authors.affiliation: Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain. cristina.hernandez@vhir.org
authors.forename: Cristina
authors.initials: C
authors.lastname: Hernández
authors.forename: Marta
authors.initials: M
authors.lastname: García-Ramírez
authors.forename: Lidia
authors.initials: L
authors.lastname: Corraliza
authors.forename: Jimena
authors.initials: J
authors.lastname: Fernández-Carneado
authors.forename: Josep
authors.initials: J
authors.lastname: Farrera-Sinfreu
authors.forename: Berta
authors.initials: B
authors.lastname: Ponsati
authors.forename: Agueda
authors.initials: A
authors.lastname: González-Rodríguez
authors.forename: Angela M
authors.initials: AM
authors.lastname: Valverde
authors.forename: Rafael
authors.initials: R
authors.lastname: Simó
mesh_terms: D000287:Administration, Topical; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology*; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D013004:Somatostatin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D013004:Somatostatin; D053148:Caspase 3; D053181:Caspase 8