Manganese transport in the rat optic nerve evaluated with spatial- and time-resolved magnetic resonance imaging

Abstract

Purpose: 1) To evaluate a novel theoretical model for in vivo axonal Mn2+ transport with MRI data from the rat optic nerve (ON); and 2) to compare predictions from the new model with previously reported experimental data. Materials and Methods: Time-resolved in vivo T1-weighted magnetic resonance imaging (MRI) of adult female Sprague-Dawley rat (n = 9) ON was obtained at different timepoints after intravitreal MnCl2 injection. A concentration-dependent and a rate-dependent function for the Mn2+ retinal ganglion cell (RGC) axon entrance was convolved with three different transport functions and each model system was optimized to fit the ON data. Results: The rate-limited input function gave a better fit to the data than the concentration-limited input. Simulations showed that the rate-limited input leads to a semilogarithmic relationship between injected dose and Mn2+ concentration in the ON, which is in agreement with previously reported in vivo experiments. A random walk transport model and an anterograde predominant slow model gave a similar fit to the data, both better than an anterograde predominant fast model. Conclusion: The results indicate that Mn2+ input into RGC axons is limited by a maximum entrance rate into the axons. Also, a wide range of apparent Mn2+ transport rates seems to be involved, different from synaptic vesicle transport rates, meaning that manganese does not depict synaptic vesicle transport rates directly. © 2010 Wiley-Liss, Inc.