A preliminary study determined an application of manganese ion eyedrops in tracing observation of visual system in vivo, but whether manganese ion has toxic effects on ocular anterior segment tissues is still unclear.

This study was to investigate the toxic effects of different concentrations of manganese ion eyedrops on ocular anterior segment tissues.

Thirty-two clean New-Zealand white rabbits were divided into 1.00 mol/L MnCl₂ group, 0.50 mol/L MnCl₂ group, 0.25 mol/L MnCl₂ group and normal control group according to random number table.The experimental eye was randomly chosen from each rabbit for eyedrops application.The manganese ion eyedrops at concentration of 1.00 mol/L, 0.50 mol/L or 0.25 mol/L was topically administered in any lateral eye of each rabbit in the 1.00 mol/L MnCl₂ group, 0.50 mol/L MnCl₂ group, 0.25 mol/L MnCl₂ group, and normal saline solution was used in the same way in the normal control group.In 2 hours, 1 day and 3, 7, 14, 21, 28 days after eyedrops application, the irritative response of ocular surface was examined under the slit lamp microscope, and corneal damage was evaluated by corneal fluorescence staining, and corneal endothelial cell density (ECD) and corneal thickness were assessed using corneal specular microscope.The eyeball samples were prepared in 3, 7, 14 and 28 days after eyedrops application and hematoxylin and eosin staining was performed for histopathological examination of conjunctiva, cornea, trabecular meshwork and ciliary body tissue.The use and care of experimental animals complied with the Statement of ARVO.

Severe hyperemia and edema in palpebral conjunctiva appeared in the 1.00 mol/L MnCl₂ group and 0.50 mol/L MnCl₂ group, and the symptoms reached a maximum level 1 day after eyedrop application and disappeared 7 days after eyedrops application in the 1.00 mol/L MnCl₂ group.These symptoms were milder in the 0.50 mol/L MnCl₂ group in comparison with the 1.00 mol/L MnCl₂ group.There were no ocular irritative response in the 0.25 mol/L MnCl₂ group.Significant differences were found in the corneal fluorescence scores among the groups 2 hours, 1 day, 3 and 7 days after eyedrop application (χ²=17.350, 19.200, 12.200, 10.140, all at P<0.05), with the highest score in the 1.00 mol/L MnCl₂ group.The ECD was not significantly different among the groups and different time points (F_group=0.38, P>0.05; F_time=1.79, P>0.05). The corneal thickness value was significantly different among the groups and different time points (F_group=18.22, P<0.05; F_time=116.75, P<0.05). The corneal thickness value was elevated during 2 hours to 3 days after administration of eyedrops in the 1.00 mol/L MnCl₂group and closed to normal from 7 days to 28 days.The corneal thickness value was higher from 2 hours to 14 days than that in 28 days after administration of eyedrops in the 1.00 mol/L MnCl₂group, and the corneal thickness value was higher in 2 hours to 1 day than that in 28 days after administration of eyedrops in the 0.50 mol/L MnCl₂group (all at P<0.05). Inflammatory cell infiltration and stromal edema were exhibited in conjunctival, trabecular meshwork and ciliary body tissue in the 1.00 mol/L MnCl₂ group 3 days and 7 days after eyedrops application, and only inflammatory cell infiltration in conjunctival tissue in the 0.50 mol/L MnCl₂ group 3 days after eyedrops application.No obvious abnormity was seen in the 0.25 mol/L MnCl₂ group.

1.00 mol/L manganese ion eyedrops has a remarkable toxic effect on ocular anterior segment tissue in rabbit.With the lowing of drug concentrations, the toxic effects were reduced.The manganese-enhanced MRI using 0.25 mol/L manganese ion eyedrops is feasibility bacause of its non-toxicity to ocular tissues.

Manganese compounds/administration & dosage; Eye drops; Administration, topical; Ocular surface; Anterior segment; Toxicity; Rabbits