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

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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.

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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

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Acknowledgments

This work was supported by the Portuguese Foundation for Science and Technology (FCT) with an individual grant to S Simão (SFRH/BPD/78404/2011), DF Santos (PD/BD/114251/2016) and GA Silva (EXPL-BIM-MEC-1433-2013), Research Center Grant UID/BIM/04773/2013 (CBMR), iNOVA4Health-UID/Multi/04462/2013, a program financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement. Also acknowledged is PIRG05-GA-2009-249314–EyeSee (Grant to GA Silva).

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Authors and Affiliations

  1. Centre for Biomedical Research (CBMR), University of Algarve, Campus Gambelas, 8005-139, Faro, Portugal

    Sónia Simão

  2. CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo Mártires da Pátria 130, 1169-056, Lisbon, Portugal

    Sónia Simão & Gabriela A. Silva

  3. ProRegeM PhD Program, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo Mártires da Pátria 130, 1169-056, Lisbon, Portugal

    Daniela F. Santos

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  1. Sónia Simão
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  2. Daniela F. Santos
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  3. Gabriela A. Silva
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Correspondence to Gabriela A. Silva.

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Simão, S., Santos, D.F. & Silva, G.A. Aliskiren decreases oxidative stress and angiogenic markers in retinal pigment epithelium cells. Angiogenesis 20, 175–181 (2017). https://doi.org/10.1007/s10456-016-9526-5

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