Role of Adenosine Receptor A2A in Traumatic Optic Neuropathies
Annual rept. 1 Dec 2011-30 Nov 2012
AUGUSTA STATE UNIV GA
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Our goal is to develop an early therapeutic intervention before the progression of traumatic optic neuropathy TON, a vision-threatening complication in head injury, becomes irreversible. Under the stress of TON, extracellular levels of adenosine increase due to its increased formation by ecto-5 -nucleotidase CD73 or decreased metabolism by the intracellular adenosine kinase AK. Intracellular adenosine is then released through equilibrative nucleoside transporter ENT. Extracellular adenosine activates an anti-inflammatory pathway through adenosine receptor A2AAR. TON is likely due to an imbalance in adenosine formation and metabolism. We report here how we determine whether AK or CD73 contributes in causing this imbalance. We have demonstrated that hypoxia-induced microglia activation is inhibited by inhibitors of MAP Kinases ERK and P38 or AK. We have also shown that hypoxia-induced CD73 up-regulation suppresses microglia activation. We now tested the hypothesis that in an in vivo model of TON at least adenosine metabolism by AK contributed to this imbalance.
- Anatomy and Physiology
- Medicine and Medical Research
- Organic Chemistry