Microglial activation in a rat model of NAION

Purpose Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common optic neuropathy over 50 years and there is no treatment for this condition. Activation of retinal microglial cells (RMC) is known to contribute to retinal ganglion cell (RCG) death after optic nerve injury. The purpose of this study was to examine early microglial activation and investigate the effect of minocycline on this activation in a rat model of NAION (rNAION). Methods We used a rNAION model to generate axonal ischemic infarct by rose Bengal dye laser photoactivation. NAION was induced in the right eye of each animals. 1 group received minocycline (22 mg/kg) intraperitoneally and the other had a sham injection of saline, 3 days before induction till sacrifice. Animals were euthanazied at day1, 3 and 7. Immunohistochemistry and quantitative stereology of RCG and RMC were performed on flat‐mounted retina. Expression levels of apoptosis‐related genes (Bax, caspase 3), inflammation related genes (IL‐1β, TNFα), and vascular growth factor related genes (VEGF‐a, VEGF‐R1, VEGF‐R2) were measured by qPCR. Results Microglia was activated early in the course of NAION. Quantitative analyses showed that the RMC number was increased in the right eye at day 1, 3, and 7 in both groups. Animals untreated tend to have increased activated RMC compared to controls (p>0.05). Minocycline also modulates proinflammatory cytokines expression, and caspase 3 activation. Conclusion Our results suggest that microglial activation contribute to retinal ganglion cell death after NAION. Minocycline may promote RGC survival by microglial inhibition.