Abstract： Background:Manganese-enhanced magnetic resonance imaging (MEMRI) for visual pathway imaging via topical administration requires further research.This study investigated the permeability of the corneal epithelium and corneal toxicity after topical administration of Mn2+ to understand the applicability of MEMRI.Methods:Forty New Zealand rabbits were divided into 0.05 mol/L,0.10 mol/L,and 0.20 mol/L groups as well as a control group (n =10 in each group).Each group was further subdivided into epithelium-removed and epithelium-intact subgroups (n =5 in each subgroup).Rabbits were given 8 drops of MnC12 in 5 min intervals.The Mn2+ concentrations in the aqueous and vitreous humors were analyzed using inductively coupled plasma-mass spectrometry at different time points.MEMRI scanning was carried out to image the visual pathway after 24 h.The corneal toxicity of Mn2+ was evaluated with corneal imaging and pathology slices.Results:Between the aqueous and vitreous humors,there was a 10 h lag for the peak Mn2+ concentration times.The intraocular Mn2+ concentration increased with the concentration gradients of Mn2+ and was higher in the epithelium-removed subgroup than that in the epithelium-intact subgroup.The enhancement of the visual pathway was achieved in the 0.10 mol/L and 0.20 mol/L epithelium-removed subgroups.The corresponding peak concentrations of Mn2+ were 5087 ± 666 ng/ml,22920 ± 1188 ng/ml in the aqueous humor and 884 ± 78 ng/ml,2556 ± 492 ng/ml in the vitreous body,respectively.Corneal injury was evident in the epithelium-removed and 0.20 mol/L epithelium-intact subgroups.Conclusions:The corneal epithelium is a barrier to Mn2+,and the iris and lens septum might be another intraocular barrier to the permeation of Mn2+.An elevated Mn2+ concentration contributes to the increased permeation of Mn2+,higher MEMRI signal,and corneal toxicity.The enhancement of the visual pathway requires an effective Mn2+ concentration in the vitreous body.