May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Hydroxyl Radical Induced [Ca2+]I Increase Is Mediated by the Reverse Mode of NCX1 in Retinal Pigment Epithelium
Author Affiliations & Notes
  • O. Zeitz
    Klinik und Poliklinik fuer Augenheilkunde, Universitaetsklinikum Hamburg-Eppendorf, Hamburg, Germany
  • L. Schlichting
    Klinik und Poliklinik fuer Augenheilkunde, Universitaetsklinikum Hamburg-Eppendorf, Hamburg, Germany
  • O. Strauss
    Klinik und Poliklinik fuer Augenheilkunde, Universitaetsklinikum Hamburg-Eppendorf, Hamburg, Germany
    Augenklinik, Universitaetsklinkum Regensburg, Regensburg, Germany
  • Footnotes
    Commercial Relationships  O. Zeitz, None; L. Schlichting, None; O. Strauss, None.
  • Footnotes
    Support  Claere Jung Foundation
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2010. doi:https://doi.org/
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      O. Zeitz, L. Schlichting, O. Strauss; Hydroxyl Radical Induced [Ca2+]I Increase Is Mediated by the Reverse Mode of NCX1 in Retinal Pigment Epithelium. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2010. doi: https://doi.org/.

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

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Abstract
 
Purpose:
 

An increased oxidative exposure of the retinal pigment epithelium (RPE) is hypothesized to play an important role in the genesis of age-related macular degeneration (ARMD). Oxidative cell damage might be mediated by a disturbance of the Ca2+-homeostasis, which leads to functional changes and apoptosis. In the present study, the reverse mode of the NCX1 is studies as a potential Ca2+ entry route after hydroxyl radical (OH- ) stimulation.

 
Methods:
 

All experiments were performed using the human RPE cell line ARPE-19. The intracellular Ca2+-content was determined by implementing the Fura-2 method. The cells were exposed for 5 minutes with OH- twice with an interval of 1h between. OH- radicals were created via the Fenton reaction using H2O2 and Fe3+. One of both OH- exposures was done in presence and one in absence of KB-R7943, which blocks the reverse mode of the NCX1, or nifedipine, a L-type Ca2+ channel blocker. For control purposes the cells were exposed twice to OH- without adding any pharmacological compound (sham control).

 
Results:
 

: Immediately after the onset of radical exposure the ARPE-19 cells showed a steep transient Ca2+-peak. The amplitude of this Ca2+-increase is significantly reduced in the presence of KB-R7943, while in the nifedipine and the sham control group the second Ca2+-peak amplitude is not reduced but even slightly increased (for quantitative results please refer to the table).

 
Conclusions:
 

Oxidative exposure of cultured RPE cells leads to a transient increased intracellular Ca2+ load. This increase is mediated by the reverse mode of the NCX1. This might be a potential target for future therapy since oxidative stress is thought to be one of the major risk factors for ARMD and disturbed Ca2+ handling might lead to various cellular dysfunctions. The latter may include altered phagocytosis activity as well as changes in gene expression pattern and apoptosis.  

 
Keywords: calcium • retinal pigment epithelium • oxidation/oxidative or free radical damage 
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