June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
Activation of the retinal renin angiotensin system via beta-adrenergic stimulation of renin expression in the RPE
Author Affiliations & Notes
  • Olaf Strauss
    Experimental Ophthalmology, Charite, University Medicine, Eye Hospital, Berlin, Germany
  • Vladimir Todorov
    Nephrology, Inner Medicine III, University Carl Gustav Carus, Dresden, Germany
  • Julia Stindl
    Experimental Ophthalmology, Eye Hospital, University Medicine Regensburg, Regensburg, Germany
  • Joana Martins
    Institute of cellular and molecular pharmacology, Sophia Antipolis University of Nice, Nice, France
  • Footnotes
    Commercial Relationships Olaf Strauss, None; Vladimir Todorov, None; Julia Stindl, None; Joana Martins, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 6100. doi:
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      Olaf Strauss, Vladimir Todorov, Julia Stindl, Joana Martins; Activation of the retinal renin angiotensin system via beta-adrenergic stimulation of renin expression in the RPE. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6100.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: The local renin-angiotensin system (RAS) in the retina plays a pivotal role in the etiology of retinal degeneration in diseases such as diabetic retinopathy or age-related macular degeneration. However, in many elderly patients, systemic factors such as the sympathetic nerve activity are changed which might have an impact in the intraocular RAS. The purpose of this study is to investigate the role of the sympathetic nerve system in the modulation of the retinal RAS.

Methods: Immunohistological analysis of the presence of sympathetic nerve endings in the choroid and in vitro analysis of renin gene expression in porcine RPE cells; renin expression in the retinal pigment epithelium (RPE) was measured in situ in mice treated with isoproterenol.

Results: Immunohistologic staining of tyrosine hydroxylase (TH) in retina sections of the mouse showed clusters of TH positive cells in the choroid in the close proximity to the RPE and few TH positive amacrine cells. Systemic administration of isoproterenol (beta-adrenoreceptor agonist) in mice leads to an up-regulation of renin mRNA expression in the RPE whereas it remains unchanged in the neuronal retina. In the presence of the systemically applied AngII receptor blocker losartan isoproterenol did not change the renin expression either in the RPE or in the retina. RT-PCR revealed the expression of all three subtypes of beta-adrenergic receptors in the retina as well as in the RPE. Cultured porcine RPE cells also showed the expression of the three known isoforms of beta-adrenergic receptors. Direct stimulation of the cAMP second-messenger system by using a combination of the phosphodiesterase inhibitor IBMX (100 µM) and the adenylate cyclase activator forskolin (5 µM) led to a strong activation of the renin expression in cultured RPE cells.

Conclusions: In summary RPE cells express beta-adrenergic receptors which could be stimulated by systemic administration of isoproterenol. The beta-adrenergic regulation of the renin expression interferes with the systemic AngII. The beta-adrenergic stimulation of the renin expression in the RPE is due to activation of the cAMP as second-messenger. Since we showed the presence of sympathetic nerve endings close to the RPE we conclude that the local RAS is under influence of the sympathetic nerve system.

Keywords: 701 retinal pigment epithelium • 412 age-related macular degeneration • 499 diabetic retinopathy  

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