title: Effects of the neuroprotective drugs somatostatin and brimonidine on retinal cell models of diabetic retinopathy.
abstract: OBJECTIVE
  Diabetic retinopathy is considered a microvascular disease, but recent evidence has underlined early involvement of the neuroretina with interactions between microvascular and neural alterations. Topical administration of somatostatin (SST), a neuroprotective molecule with antiangiogenic properties, prevents diabetes-induced retinal neurodegeneration in animals. The α2-adrenergic receptor agonist brimonidine (BRM) decreases vitreoretinal vascular endothelial growth factor and inhibits blood-retinal barrier breakdown in diabetic rats. However, SST and BRM effects on microvascular cells have not yet been studied. We investigated the behaviour of these drugs on the crosstalk between microvasculature and neuroretina.
  
  
  METHODS
  Expression of SST receptors 1-5 in human retinal pericytes (HRP) was checked. We subsequently evaluated the effects of diabetic-like conditions (high glucose and/or hypoxia) with/without SST/BRM on HRP survival. Endothelial cells (EC) and photoreceptors were maintained in the above conditions and their conditioned media (CM) used to culture HRP. Vice versa, HRP-CM was used on EC and photoreceptors. Survival parameters were assessed.
  
  
  RESULTS
  HRP express the SST receptor 1 (SSTR1). Glucose fluctuations mimicking those occurring in diabetic subjects are more damaging for pericytes and photoreceptors than stable high glucose and hypoxic conditions. SST/BRM added to HRP in diabetic-like conditions decrease EC apoptosis. However, neither SST nor BRM changed the response of pericytes and neuroretina-vascular crosstalk under diabetic-like conditions.
  
  
  CONCLUSIONS
  Retinal pericytes express SSTR1, indicating that they can be a target for SST. Exposure to SST/BRM had no adverse effects, direct or mediated by the neuroretina, suggesting that these molecules could be safely evaluated for the treatment of ocular diseases.
authors.affiliation: Department of Medical Sciences, University of Turin, Corso AM Dogliotti 14, 10126, Turin, Italy. elena.beltramo@unito.it.
authors.forename: Elena
authors.identifier: http://orcid.org/0000-0002-7868-0988
authors.initials: E
authors.lastname: Beltramo
authors.affiliation: Department of Medical Sciences, University of Turin, Corso AM Dogliotti 14, 10126, Turin, Italy.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Lopatina
authors.affiliation: Department of Medical Sciences, University of Turin, Corso AM Dogliotti 14, 10126, Turin, Italy.
authors.forename: Aurora
authors.initials: A
authors.lastname: Mazzeo
authors.affiliation: Alberto Sols Biomedical Research Institute (IIBm) (CSIC/UAM), C/Arturo Duperier 4, 28029, Madrid, Spain.|Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERdem), ISCIII, Instituto de Salud Carlos III, C/Monforte de Lemos 3-5, 28029, Madrid, Spain.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Arroba
authors.affiliation: Alberto Sols Biomedical Research Institute (IIBm) (CSIC/UAM), C/Arturo Duperier 4, 28029, Madrid, Spain.|Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERdem), ISCIII, Instituto de Salud Carlos III, C/Monforte de Lemos 3-5, 28029, Madrid, Spain.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Valverde
authors.affiliation: Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERdem), ISCIII, Instituto de Salud Carlos III, C/Monforte de Lemos 3-5, 28029, Madrid, Spain.|Diabetes and Metabolism Research Unit, Institut de Recerca Hospital Universitari Vall d'Hebron (VHIR), Pg. Vall d'Hebron 119-129, 08035, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Hernández
authors.affiliation: Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERdem), ISCIII, Instituto de Salud Carlos III, C/Monforte de Lemos 3-5, 28029, Madrid, Spain.|Diabetes and Metabolism Research Unit, Institut de Recerca Hospital Universitari Vall d'Hebron (VHIR), Pg. Vall d'Hebron 119-129, 08035, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Simó
authors.affiliation: Department of Medical Sciences, University of Turin, Corso AM Dogliotti 14, 10126, Turin, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Porta
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D020286:Pericytes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017481:Receptors, Somatostatin / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D055351:Retinal Neurons / Q000187:drug effects*; D013004:Somatostatin / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D018696:Neuroprotective Agents; D017481:Receptors, Somatostatin; D042461:Vascular Endothelial Growth Factor A; C101130:somatostatin receptor type 1; D000068438:Brimonidine Tartrate; D013004:Somatostatin
keywords: Brimonidine; Diabetic retinopathy; Endothelial cell; Pericyte; Photoreceptor cell; Somatostatin