April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
The Activation Of A3 Adenosine Receptor Inhibits Retinal Ganglion Cell Apoptosis
Author Affiliations & Notes
  • Joana M. Galvao
    Visual Neuroscience, UCL Institute of Ophthalmology, London, United Kingdom
    Center of Ophthalmology and Vision Sciences, IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
  • Eduardo M. Normando
    Visual Neuroscience, UCL Institute of Ophthalmology, London, United Kingdom
    Western Eye Hospital, London, United Kingdom
  • Li Guo
    Visual Neuroscience, UCL Institute of Ophthalmology, London, United Kingdom
  • Ana R. Santiago
    Center of Ophthalmology and Vision Sciences, IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
  • Antonio F. Ambrosio
    Center of Ophthalmology and Vision Sciences, IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
  • M F. Cordeiro
    Glauc & Ret Neurodegeneration Res Grp, UCL Inst Ophthal & Western Eye Hsp, London, United Kingdom
  • Footnotes
    Commercial Relationships  Joana M. Galvao, None; Eduardo M. Normando, None; Li Guo, None; Ana R. Santiago, None; Antonio F. Ambrosio, None; M. F. Cordeiro, None
  • Footnotes
    Support  FCT – Foundation for Science and Technology, Portugal (fellowship SFRH/BD/47947/2008).
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 3087. doi:https://doi.org/
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      Joana M. Galvao, Eduardo M. Normando, Li Guo, Ana R. Santiago, Antonio F. Ambrosio, M F. Cordeiro; The Activation Of A3 Adenosine Receptor Inhibits Retinal Ganglion Cell Apoptosis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3087. doi: https://doi.org/.

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

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Abstract

Purpose: : Adenosine receptors have been considered potential therapeutic targets in neurodegenerative diseases. In the retina, adenosine and three of its four receptors have been identified at the level of retinal ganglion cells (RGCs). In this study, we focused on assessing the A3 receptor and its modulation using the A3 agonist, 2-Cl-IB-MECA, in a rat model of RGC apoptosis.

Methods: : Chronic ocular hypertension (OHT) was induced in one eye of Dark Agouti rats, with the opposite eye as control, using our established technique. Immunohistological analysis of A3 adenosine receptor expression was performed in 5 µm thick paraffin sections from enucleated eyes. The potential neuroprotective effect of the A3 adenosine receptor agonist 2-Cl-IB-MECA was assessed using three different concentrations (1.2 µM, 6 µM and 12 µM) in a model of chemical induced RGC apoptosis (intravitreal injection of 8% DMSO was used in Dark Agouti rats). The eyes were imaged 2h after the injection using DARC (Detection of Apoptosis in Retinal Cells) with methods and analysis we have previously described.

Results: : Immunohistology confirmed the presence of the A3 adenosine receptor in RGC layer. However, the expression of A3 adenosine receptor was down regulated in the OHT eyes compared to control (p<0.05). DARC imaging showed that the A3 adenosine receptor agonist 2-Cl-IB-MECA significantly reduced RGC apoptosis compared to control at 1.2 µM (p<0.05) and 6 µM (p<0.05) concentrations. Decreased levels of RGC apoptosis were quantified as 69.9% (1.2 µM), 76.5% (6 µM) and 24.5% (12 µM), compared to untreated control.

Conclusions: : These results suggest that the A3 adenosine receptor is down regulated in RGC layer by chronic OHT. Moreover, the agonist 2-Cl-IB-MECA has neuroprotective effects on RGC apoptosis in vivo. We suggest that the targeting of A3 activity and delineation of its relationship with RGC apoptosis could have great potential in the management of glaucoma, with future work needed to confirm this hypothesis.Acknowledgements to: Prof. Claire Mitchell, University of Pennsylvania, Department of Ophthalmology

Keywords: neuroprotection • apoptosis/cell death • adenosine 
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