title: Manganese-enhanced MRI optic nerve tracking: effect of intravitreal manganese dose on retinal toxicity.
abstract: The aim of this study was to provide data on the dose dependence of manganese-enhanced MRI (MEMRI) in the visual pathway of experimental rats and to study the toxicity of MnCl₂ to the retina. Sprague-Dawley rats were intravitreally injected with 2 μL of 0, 10, 25, 50, 75, 100, 150 and 300 mM MnCl₂, respectively. The contrast-to-noise ratio (CNR) of MEMRI for optic nerve enhancement was measured at different concentrations of MnCl₂. Simultaneously, the toxicity of manganese was evaluated by counting retinal ganglion cells and by retinal histological examination using light microscopy and transmission electron microscopy. The CNR increased with increasing concentration of MnCl₂ up to 75 mM. Retinal ganglion cell densities were reduced significantly when the concentration of MnCl₂ in the intravitreal injection was equal to or greater than 75 mM. Increasing numbers of ribosomes in retinal ganglion cells were first detected at 25 mM of MnCl₂. The retinal toxicity of MnCl₂ at higher concentration also included mitochondrial pathology and cell disruption of retinal ganglion cells, as well as abnormalities of photoreceptor and retinal pigment epithelium cells. It can be concluded that intravitreal injection of MnCl₂ induces retinal cell damage that appears to start from 25 mM. The concentration of MnCl₂ should not exceed 25 mm through intravitreal injection for visual pathway MEMRI in the rat.
authors.affiliation: Peking University Eye Center, Peking University Third Hospital, Beijing, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Luo
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Zhaodong
authors.initials: Z
authors.lastname: Du
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Ma
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000818:Animals; D002452:Cell Count; D002712:Chlorides / Q000008:administration & dosage* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D058449:Intravitreal Injections; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D017895:Manganese Compounds / Q000008:administration & dosage*; D009900:Optic Nerve / Q000187:drug effects* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D059629:Signal-To-Noise Ratio
chemical_list: D002712:Chlorides; D017895:Manganese Compounds; C025340:manganese chloride