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Anne-Laure Remond, Audrey Fel, Manuel SIMONUTTI, Ivana IVKOVIC, Jose Alain Sahel, Phuc LeHoang, Bahram Bodaghi, Serge A Picaud, Valerie Touitou; Microglial activation in a rat model of NAION. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5542.
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© ARVO (1962-2015); The Authors (2016-present)
Non arteritic anterior ischemic optic neuropathy (NAION) is the most common optic neuropathy over 50 years and its pathophysiology remains controversial. 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 investigate early microglial activation and the effect of minocycline on this activation in a rat model of NAION (rNAION).
We used a rNAION model to generate axonal ischemic infarct by rose Bengal dye laser photoactivation. NAION was induced in the right eye (RE) of each animal. One group of animals received minocycline (22 mg/kg) intraperitoneally and a second group received a sham injection of saline, 3 days before induction till sacrifice. Animals were euthanazied at day 1, 3 and 7 after laser photoactivation. Immunohistochemistry and quantitative stereology of RCG (Brn3a positive cells) and RMC (IBA-1positive cells) were performed on flat-mounted retina. Expression levels of IBA-1, apoptosis-related genes (Bax, caspase 3) and vascular growth factor related genes (VEGF-a) were measured by qPCR.
A significant increase in the number of RMC was observed with stereology on flat-mounted retina in eyes with NAION, at day 1, 3 and 7 after induction. The expression of Iba-A, a microglia/macrophage-specific calcium-binding protein, measured by qPCR, was statistically increased in the eyes with NAION, at day 3 for both groups (minocycline and saline) and at day 7 for the group treated with minocycline (p<0,05). This expression was higher with minocycline at day 3 and 7. The expression of caspase was significantly increased (p <0.05) in NAION eyes at day 3 in the group treated with minocycline and VEGF-A tended to have an increased expression in the group with saline at day 3 and 7 (p>0.05). There was no difference in the expression of Bax between the two groups.
Our results demonstrate that microglia is activated early in the course of NAION and contribute to retinal ganglion cell death after NAION. The presence of an increased number of activated microglial cells in the eyes with NAION of animals treated with minocyclin is unexpected considering the supposed effect of minocyclin. However, microglial cells include a broad spectrum of populations and minocycline could modulate one of these sub-populations with a protective effect on ganglion cells after the stroke thus promoting RGC survival.
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