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D. Inman, A. Bosco, M. R. Steele, G. Wu, D. J. Calkins, P. J. Horner, M. L. Vetter; Chronic Minocycline Treatment Decreases Microglial Activation and Improves Retrograde Axonal Transport in Retinal Ganglion Cells in DBA/2J Retina. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3291.
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Retinal microglia have been implicated in the pathogenesis of glaucoma. Minocycline is a tetracycline derivative with a documented inhibitory effect on microglial activation. This study sought to determine the effect of daily minocycline treatment on the glaucomatous changes in the DBA/2J mouse retina.
DBA/2J mice received daily gavage of minocycline (120mg/kg) from 2 to 7.5 months of age and age-matched control mice received vehicle. IOP was measured 7 times over the course of the experiment. One week prior to sacrifice, a sub-group of mice received FluoroGold injection (1%) to retrogradely label ganglion cells. Retinas were processed for RNA and histology and optic nerves for electron microscopy.
IOP was similarly elevated in both control and experimental groups. No differences in numbers of NeuN+ neurons, GFAP+ astrocytes, or Iba1+ microglia were observed in wholemount preparations of control and experimental retina. There was a significant decrease in the number of FG+ ganglion cells in control retina, suggesting that minocycline had a positive effect on axon transport in experimental retina. Furthermore, the minocycline-treated group demonstrated a significant shift to larger axonal areas at 5 months. An analysis of microglial morphology demonstrated a trend toward greater ramification for minocycline treated microglia and a significant decrease in Iba1 labeling intensity, indicating decreased microglial activation.
Our data suggests that systemic minocycline treatment exerts an inhibitory effect on retinal microglia as demonstrated by fewer phagocytic microglia in minocycline retina. This was correlated with significant improvement of retrograde axonal transport and rescue of large axonal loss, suggesting improved retinal ganglion cell viability in the DBA/2J retina with minocycline treatment.
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