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M. J. Ogidigben, A. Coimbra, R. Peiffer, L. A. O'Neill-Davis, D. Welsh, X. Meng; Brain Derived Neurotrophic Factor (BDNF) Preserved Axonal Transport After Optic Nerve Crush in Rat: Manganese-Enhanced MRI Study. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4221.
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Optic nerve lesion or radiation has been shown to stop manganese active anterograde axonal transport in the rat visual system. This study was conducted to evaluate the effect of BDNF on axonal transport following intravitreal injection of manganese in a rat optic nerve crush model.
15 Wister rats of either sex were divided into three groups of 5. The optic nerves of rats in groups 1 and 2 were crushed unilaterally and the nerve crushed eyes were injected with BDNF (1uM) or vehicle. Contralateral eyes received vehicle, intravitreally. On day 9, all animals in groups 1 and 2 were injected intravitreally with manganese chloride in the optic nerve crushed eyes. In addition, the remaining five rats in group 3 received unilateral intravitreal manganese as controls. MRI imaging was conducted 24 hours after Mn injection. A high resolution T1 weighted 3D FLASH sequence was acquired with TR/TE/NEX=[28/1.26/2], FOV=30x30x30 mm3 and matrix=150x150x150 parameters. Optic nerve cross-sections at intervals of 0.2 mm from 0-2.5 mm from the optic nerve head was used to calculate image intensity and manganese enhancement.
24 hours after intravitreal injection of manganese MRI produced a clear enhanced image of the optic nerve from the retina to superior colliculus in controls (n=5). In contrast, manganese accumulated in the eye and optic nerve region before the crush site 2-3 mm from the globe in rats with crushed optic nerves (n=5). Pretreatment with intravitreal BDNF minimized the manganese accumulation in crushed eyes.
Our results suggest that BDNF prevented impaired manganese axonal active transport in rat eyes with crushed optic nerve suggesting that BDNF rescues ganglion cells, in part, by preserving axonal transport. A longitudinal study is required to evaluate the long term effects of intravitreal BDNF on the visual pathway.
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