July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Adenosine A3 receptor agonist prevents the loss of retinal ganglion cells in a glaucoma model
Author Affiliations & Notes
  • Raquel Boia
    Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal
    CNC.IBILI Consortium, University of Coimbra, Portugal
  • Manuel Salinas-Navarro
    Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Spain
    Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain, Spain
  • Alejandro Gallego-Ortega
    Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Spain
    Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain, Spain
  • Caridad Galindo-Romero
    Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Spain
    Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain, Spain
  • Marta Agudo-Barriuso
    Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Spain
    Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain, Spain
  • Antonio F Ambrosio
    Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal
    CNC.IBILI Consortium, University of Coimbra, Portugal
  • Manuel Vidal-Sanz
    Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, Spain
    Instituto Murciano de Investigación Biosanitaria-Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain, Spain
  • Ana Raquel Santiago
    Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal
    CNC.IBILI Consortium, University of Coimbra, Portugal
  • Footnotes
    Commercial Relationships   Raquel Boia, None; Manuel Salinas-Navarro, None; Alejandro Gallego-Ortega, None; Caridad Galindo-Romero, None; Marta Agudo-Barriuso, None; Antonio Ambrosio, None; Manuel Vidal-Sanz, None; Ana Raquel Santiago, None
  • Footnotes
    Support  FCT (PD/BD/114115/2015, Grant PTDC/NEU-OSD/3123/2014 and Strategic Project UID/NEU/04539/2013), FEDER-COMPETE (FCOMP-01-0124-FEDER-028417 and POCI-01-0145-FEDER-007440) and Centro 2020 Regional Operational Programme (CENTRO-01-0145-FEDER-000008: BrainHealth 2020), Portugal.
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 625. doi:
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    • Get Citation

      Raquel Boia, Manuel Salinas-Navarro, Alejandro Gallego-Ortega, Caridad Galindo-Romero, Marta Agudo-Barriuso, Antonio F Ambrosio, Manuel Vidal-Sanz, Ana Raquel Santiago; Adenosine A3 receptor agonist prevents the loss of retinal ganglion cells in a glaucoma model. Invest. Ophthalmol. Vis. Sci. 2019;60(9):625.

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

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Abstract

Purpose : Glaucoma is a leading cause of irreversible blindness and current treatments target the lowering of intraocular pressure (IOP). In some patients, vision loss progresses despite successful IOP control, indicating that new and effective treatments are needed, such as those targeting neuroprotection of retinal ganglion cells (RGCs). Adenosine A3 receptor (A3R) activation confers protection to RGCs following excitotoxic stimuli. In this work, we investigated whether the activation of A3R could also afford RGC protection in a well characterized animal model of glaucoma.

Methods : Ocular hypertension (OHT) was induced by laser photocoagulation of the limbal veins and the A3R agonist (2-Cl-IB-MECA) was delivered intravitreally immediately after surgery. The retrograde axonal transport was determined by application of Fluorogold (FG) in both superior colliculi. Electroretinography was performed after 7 days of OHT induction to assess retinal electrical activity. The survival of RGCs was assessed in whole-mounted retinas by Brn3a immunodetection.

Results : The assessment of retinal function demonstrated that OHT induced a significant decrease in scotopic threshold response (STR), a- and b-wave amplitudes. The A3R agonist prevented the alterations induced by OHT in STR (p<0.05), without changing a- and b-wave amplitudes in scotopic conditions. Moreover, the treatment with the A3R agonist significantly decreased the loss of RGCs induced by OHT (p<0.05) and attenuated the impairment in retrograde axonal transport induced by OHT.

Conclusions : Our results show that 2-Cl-IB-MECA increased the RGC survival in OHT animals. Taking into consideration the beneficial effect of A3R agonist, we can envisage that A3R can be considered a good therapeutic target to protect RGCs from glaucomatous damage.

Support: FCT (PD/BD/114115/2015, Grant PTDC/NEU-OSD/3123/2014 and Strategic Project UID/NEU/04539/2013), FEDER-COMPETE (FCOMP-01-0124-FEDER-028417 and POCI-01-0145-FEDER-007440) and Centro 2020 Regional Operational Programme (CENTRO-01-0145-FEDER-000008: BrainHealth 2020), Portugal.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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