Adenosine kinase as a therapeutic target in traumatic optic neuropathy

Abstract

Background The purpose of this study is to understand the mechanism of traumatic optic neuropathy (TON) in order to prevent vision loss. Following traumatic insults to the optic nerve, retinal microglia cells are activated through MAP Kinase pathways and increased cytotoxic activity that causes retinal ganglion cell death [1]. Under stress condition, extracellular concentration of adenosine is likely to increase and activates an anti-inflammatory pathway through A2A adenosine receptor. But in TON, the accumulated extracellular adenosine is then transported intracellular through equilibrative nucleoside transporters (ENTs) which further gets converted into AMP by Adenosine kinase (AK), which results in low extracellular adenosine concentration. We have demonstrated that microglia activation and TNF-a release was inhibited by AK inhibitor. Based on these findings, we hypothesize that an imbalance in adenosine formation and metabolism in the retinal microglia participated by AK may contribute significantly to retinal complications in the setting of TON.