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R. S. Zulliger, S. Eigeldinger-Berthou, U. Wolf, V. Enzmann; N-Methyl-N-Nitrosurea (MNU) Induces Concentration-Dependent Cell Death in Photoreceptors of the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2294.
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Retinitis pigmentosa (RP), a disease affecting already young people starting with night blindness and succeeding to total vision loss in most patients at the age of 60, is one of the most important pathologies in the eye. N-methyl-N-nitrosurea (MNU) can be used to selectively damage photoreceptor cells mimicking RP-like symptoms. In the present study we investigated different concentrations of MNU to study the morphological changes over time and correlated them to visual impairment.
To induce retinal degeneration MNU was applied intraperitoneally (i.p.) with 30, 35, 45, 50, 55 or 60mg/ kg bodyweight to 6-8 weeks old male C57BL6 mice. Visual function was assessed with both a cued water maze (WM) behavioral test and the optokinetic reflex (OKR) measurement at day 3, 7, 14 and 21 post injection (PI). To visualize morphological changes in the retina paraffin section (7 µm) were stained with H&E. To assess the viability of the retinal pigment epithelium (RPE), autofluorescence was measured on whole eye flat mounts with confocal laser scanning microscopy. Additionally, to detect apoptotic cells in the retina TUNEL staining was applied.
Damage in the sensory retina induced by MNU was significant already seven days PI and its extent concentration-dependent. However, the RPE layer appears to be not effected. Visual deficits were already measurable by WM and OKR three days PI. TUNEL-staining showed many apoptotic cells also three days after MNU application. The positive staining was found in the outer nuclear layer only.
After the treatment with MNU photoreceptor cells die by apoptosis while RPE cells seem to be unaffected. The damage is already visible very early on and can even lead to complete disappearance of the outer nuclear layer using high doses. To elucidate the pathway of apoptosis in photoreceptors and a possible use as a RP model, further experiments will be necessary.
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