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Effects of the neuroprotective drugs somatostatin and brimonidine on retinal cell models of diabetic retinopathy

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Abstract

Aims

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.

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Abbreviations

BRB:

Blood–retinal barrier

BRM:

Brimonidine

DMO:

Diabetic macula oedema

DR:

Diabetic retinopathy

EC:

Endothelial cells

HG:

High glucose concentrations

HMEC:

Human microvascular endothelial cells

Hypo:

Hypoxic conditions

intHG:

Intermittent high glucose concentrations

NG:

Physiological glucose concentrations

NMDA:

N-Methyl-d-aspartate

PDR:

Proliferative diabetic retinopathy

RT-PCR:

Real-time PCR

SST:

Somatostatin

SSTR:

Somatostatin receptor(s)

VEGF:

Vascular endothelial growth factor

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Acknowledgments

This research was supported by the EUROCONDOR project, Grant Agreement Number 278040, funded by the European Commission’s Seventh Framework Programme (theme FP7-HEALTH-2011.2.4.3-1). This publication reflects the views only of the Authors, and the European Commission cannot be held responsible for any use which may be made of the information contained therein.

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Authors and Affiliations

  1. Department of Medical Sciences, University of Turin, Corso AM Dogliotti 14, 10126, Turin, Italy

    Elena Beltramo, Tatiana Lopatina, Aurora Mazzeo & Massimo Porta

  2. Alberto Sols Biomedical Research Institute (IIBm) (CSIC/UAM), C/Arturo Duperier 4, 28029, Madrid, Spain

    Ana I. Arroba & Angela M. Valverde

  3. 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

    Ana I. Arroba, Angela M. Valverde, Cristina Hernández & Rafael Simó

  4. Diabetes and Metabolism Research Unit, Institut de Recerca Hospital Universitari Vall d’Hebron (VHIR), Pg. Vall d’Hebron 119-129, 08035, Barcelona, Spain

    Cristina Hernández & Rafael Simó

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  1. Elena Beltramo
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Correspondence to Elena Beltramo.

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Elena Beltramo, Tatiana Lopatina, Aurora Mazzeo, Ana I Arroba, Angela M Valverde, Cristina Hernández, Rafael Simó and Massimo Porta declare that they have no conflicts of interest.

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Beltramo, E., Lopatina, T., Mazzeo, A. et al. Effects of the neuroprotective drugs somatostatin and brimonidine on retinal cell models of diabetic retinopathy. Acta Diabetol 53, 957–964 (2016). https://doi.org/10.1007/s00592-016-0895-4

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