Adenosine kinase as a therapeutic target in traumatic optic neuropathy
© Ahmad et al; licensee BioMed Central Ltd. 2014
Published: 2 April 2014
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 . 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-α 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.
Materials and methods
Mice were anesthetized according to standard protocol and bilateral limbal conjunctival peritomy was performed posteriorly to the optic nerve in each mouse. Mice were treated with or without an AK inhibitor (AKI), ABT702 (25μg/kg; i. p.), every other day for 7 days. All retinas or eye ball were then harvested for protein, histology and RNA expression.
Based on our findings, we conclude that Adenosine Kinase inhibition may have potential role in regulating inflammatory mechanism in TON mouse model.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.