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Manganese-enhanced MRI optic nerve tracking: effect of intravitreal manganese dose on retinal toxicity
1Peking University Eye Center, Peking University Third Hospital, Beijing, China.
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.
Insights
Manganese-enhanced MRI (MEMRI) visual pathway studies in rats show retinal ganglion cell damage starting at 25 mM MnCl₂. Optimal MEMRI requires intravitreal MnCl₂ concentrations not exceeding 25 mM to avoid retinal toxicity.
Area of Science:
- Neuroimaging
- Ophthalmology
- Toxicology
Background:
- Manganese-enhanced MRI (MEMRI) is a neuroimaging technique.
- Assessing MEMRI dose dependence and retinal toxicity is crucial for visual pathway studies.
Purpose of the Study:
- Determine the dose-dependent effects of manganese chloride (MnCl₂) on visual pathway MEMRI in rats.
- Evaluate the retinal toxicity of intravitreally injected MnCl₂.
Main Methods:
- Intravitreal injections of varying MnCl₂ concentrations (0-300 mM) in Sprague-Dawley rats.
- Measurement of optic nerve contrast-to-noise ratio (CNR) for MEMRI.
- Retinal ganglion cell counting and histological examination (light and transmission electron microscopy) to assess toxicity.
Main Results:
- Optic nerve CNR increased with MnCl₂ concentration up to 75 mM.
- Significant reduction in retinal ganglion cell density observed at MnCl₂ concentrations of 75 mM and above.
- Early signs of retinal toxicity, including increased ribosomes in ganglion cells, detected at 25 mM MnCl₂.
Conclusions:
- Intravitreal MnCl₂ induces retinal cell damage, beginning at concentrations as low as 25 mM.
- For visual pathway MEMRI in rats, intravitreal MnCl₂ concentration should not exceed 25 mM to mitigate retinal toxicity.
