Impact of repeated topical-loaded manganese-enhanced MRI on the mouse visual system.
OBJECTIVE
Optic nerve degeneration in diseases such as glaucoma and multiple sclerosis evolves in months to years. The use of Mn(2+)-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 Mn(2+) delivery to the visual system. This study is to evaluate the impact of biweekly or monthly repeated Mn(2+) topical administration and the pH levels of the Mn(2+) solutions for MEMRI on the mouse visual pathway.


METHODS
Using groups of mice, the MEMRI with an acidic or pH neutralized 1 M MnCl(2) 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 Mn(2+) solution induced a greater MEMRI enhancement as compared with a neutral pH Mn(2+) solution. Significant 20% RGC loss was found after three biweekly Mn(2+) inductions, but no RGC loss was found after three monthly Mn(2+) treatments. The corneal thickness was found increased after seven biweekly topical-loaded MEMRI.


CONCLUSIONS
Acidic Mn(2+) solutions enhanced the uptake of Mn(2+) observed on the MEMRI. Increasing the time intervals of repeated Mn(2+) topical administration reduced the adverse effects caused by MEMRI.
Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA. rsun@llu.edu
Shu-Wei
SW
Sun
Tiffany
T
Thiel
Hsiao-Fang
HF
Liang
D000287:Administration, Topical; D000818:Animals; D003287:Contrast Media / Q000009:adverse effects / Q000737:chemistry; D005260:Female; D007089:Image Enhancement / Q000379:methods*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D017895:Manganese Compounds / Q000009:adverse effects / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D041623:Tomography, Optical Coherence; D014795:Visual Pathways / Q000378:metabolism / Q000473:pathology
D003287:Contrast Media; D017895:Manganese Compounds