Impact of repeated topical-loaded manganese-enhanced MRI on the mouse visual system

PURPOSE. Optic nerve degeneration in diseases such as glaucoma and multiple sclerosis evolves in months to years. The use of Mn2+-Enhanced Magnetic Resonance Imaging (MEMRI) in a time-course study may provide new insights into the disease progression. Previously, we demonstrated the feasibility of using a topical administration for Mn2+ delivery to the visual system. This study is to evaluate the impact of biweekly or monthly repeated Mn2+ topical administration and the pH levels of the Mn2+ solutions for MEMRI on the mouse visual pathway. METHODS. Using groups of mice, the MEMRI with an acidic or pH neutralized 1 M MnCl2 solution was performed. To evaluate the feasibility of repeated MEMRIs, topical-loaded MEMRI was conducted biweekly seven times or monthly three times. The enhancement of MEMRI in the visual system was quantified. After repeated MEMRIs, the corneas were examined by optical coherence tomography. The retinal ganglion cells (RGCs) and optic nerves were examined by histology. RESULTS. All mice exhibited consistent enhancements along the visual system following repeated MEMRIs. The acidic Mn2+ solution induced a greater MEMRI enhancement as compared with a neutral pH Mn2+ solution. Significant 20% RGC loss was found after three biweekly Mn2+ inductions, but no RGC loss was found after three monthly Mn2+ treatments. The corneal thickness was found increased after seven biweekly topicalloaded MEMRI. CONCLUSIONS. Acidic Mn2+ solutions enhanced the uptake of Mn2+ observed on the MEMRI. Increasing the time intervals of repeated Mn2+ topical administration reduced the adverse effects caused by MEMRI. © 2012 The Association for Research in Vision and Ophthalmology, Inc.