Potential role of A2A adenosine receptor in traumatic optic neuropathy

Saif Ahmad, Nadeem Fatteh, Nehal M. El-Sherbiny, Mohammad Naime, Ahmed S. Ibrahim, Ahmed M. El-Sherbini, Sally A. El-Shafey, Sohail Khan, Sadanand Fulzele, Joyce Gonzales, Gregory I. Liou

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24 Scopus citations

Abstract

In traumatic optic neuropathy (TON), apoptosis of retinal ganglion cells is closely related to the local production of reactive oxygen species and inflammatory mediators from activated microglial cells. Adenosine receptor A2A (A2AAR) has been shown to possess anti-inflammatory properties that have not been studied in TON. In the present study, we examined the role of A2AAR in retinal complications associated with TON. Initial studies in wild-type mice revealed that treatment with the A2AAR agonist resulted in marked decreases in the TON-induced microglial activation, retinal cell death and releases of reactive oxygen species and pro-inflammatory cytokines TNF-α and IL-6. To further assess the role of A2AAR in TON, we studied the effects of A2AAR ablation on the TON-induced retinal abnormalities. A2AAR-/- mice with TON showed a significantly higher mRNA level of TNF-α, Iba1-1 in retinal tissue, and ICAM-1 expression in retinal sections compared with wild-type mice with TON. To explore a potential mechanism by which A2AAR-signaling regulates inflammation in TON, we performed additional studies using hypoxia- or LPS-treated microglial cells as an in vitro model for TON. Activation of A2AAR attenuates hypoxia or LPS-induced TNF-α release and significantly repressed the inflammatory signaling, ERK in the activated microglia. Collectively, this work provides pharmacological and genetic evidence for A2AAR signaling as a control point of cell death in TON and suggests that the retinal protective effect of A2AAR is mediated by attenuating the inflammatory response that occurs in microglia via interaction with MAPKinase pathway.

Original languageEnglish (US)
Pages (from-to)54-64
Number of pages11
JournalJournal of Neuroimmunology
Volume264
Issue number1-2
DOIs
StatePublished - Oct 2 2013

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Keywords

  • Adenosine A receptor
  • Inflammatory cytokines
  • MAPKinase
  • Microglia
  • Oxidative stress
  • Traumatic optic neuropathy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

Cite this

Ahmad, S., Fatteh, N., El-Sherbiny, N. M., Naime, M., Ibrahim, A. S., El-Sherbini, A. M., El-Shafey, S. A., Khan, S., Fulzele, S., Gonzales, J., & Liou, G. I. (2013). Potential role of A2A adenosine receptor in traumatic optic neuropathy. Journal of Neuroimmunology, 264(1-2), 54-64. https://doi.org/10.1016/j.jneuroim.2013.09.015