Angiogenesis

, Volume 20, Issue 1, pp 175–181

Aliskiren decreases oxidative stress and angiogenic markers in retinal pigment epithelium cells

  • Sónia Simão
  • Daniela F. Santos
  • Gabriela A. Silva
Brief Communication

DOI: 10.1007/s10456-016-9526-5

Cite this article as:
Simão, S., Santos, D.F. & Silva, G.A. Angiogenesis (2017) 20: 175. doi:10.1007/s10456-016-9526-5

Abstract

There is growing evidence on the role of ocular renin–angiotensin system (RAS) in the development of diabetic retinopathy (DR), particularly due to the trigger of oxidative stress and angiogenesis. Despite this there is no effective RAS-based therapy in DR capable of preventing retinal damage induced by RAS activation. We recently described that retinal pigment epithelium (RPE) cells express the main components of the RAS. We here propose to investigate the role of glucose upon the retinal RAS and whether aliskiren, a direct renin inhibitor, protects RPE cells from angiogenesis and oxidative stress. RPE cells were chosen as target since one of the first events in DR is the dysfunction of the RPE retinal layer, which as a key function in maintaining the integrity of the retina. We found that the RAS present in the RPE cells was deregulated by hyperglycemic glucose concentrations. Exposure of RPE cells to angiotensin II increased the levels of the main pro-angiogenic factor, vascular endothelial growth factor (VEGF) in a concentration-dependent manner. Additionally, angiotensin II also stimulated the production of reactive oxygen species in RPE cells. Treatment of RPE cells with aliskiren decreased the levels of oxidative stress and promoted the expression of anti-angiogenic factors such as the pigment epithelium-derived factor and the VEGF165b isoform. Our findings demonstrate that the RAS is deregulated in hyperglycemic conditions and that aliskiren successfully protected RPE cells from RAS over activation. These anti-angiogenic and antioxidant properties described for aliskiren over RPE cells suggest that this drug has potential to be used in the treatment of diabetic retinopathy.

Keywords

Retinal pigment epithelium Aliskiren Renin–angiotensin system Angiogenesis Oxidative stress 

Abbreviations

ACE

Angiotensin II-converting enzyme

ARB

Angiotensin II receptor blocker

BRB

Blood retinal barrier

DR

Diabetic retinopathy

DRI

Direct renin inhibitor

PEDF

Pigment epithelium-derived factor

RAS

Renin–angiotensin system

ROS

Reactive oxygen species

RPE

Retinal pigment epithelium

VEGF

Vascular endothelial growth factor

Funding information

Funder NameGrant NumberFunding Note
Fundação para a Ciência e a Tecnologia
  • SFRH/BPD/78404/2011
  • PD/BD/114251/2016
  • EXPL-BIM-MEC-1433-2013
  • UID/BIM/04773/2013
  • UID/Multi/04462/2013
European Commission
  • PIRG05-GA-2009-249314

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Sónia Simão
    • 1
    • 2
  • Daniela F. Santos
    • 3
  • Gabriela A. Silva
    • 2
  1. 1.Centre for Biomedical Research (CBMR)University of AlgarveFaroPortugal
  2. 2.CEDOC, NOVA Medical School/Faculdade de Ciências MédicasUniversidade Nova de LisboaLisbonPortugal
  3. 3.ProRegeM PhD Program, NOVA Medical School/Faculdade de Ciências MédicasUniversidade Nova de LisboaLisbonPortugal

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