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C. Ren, C. Xiao, Y. Nan, B. Chen, E. Yu, M. Pu; N-Methyl-N-Nitrosourea-Induced Photoreceptor Apoptosis in Cats. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3618.
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N-Methyl-N-nitrosourea (MNU) has been widely used in rodents for inducing photoreceptor apoptosis. However, the effectiveness of the agent has not been tested in large mammals such as cat. Our goal was to evaluate impacts of MNU on photoreceptors and other retinal neurons and determine an effective dosage for this species.
Young adult cats were used in this experiment. MNU was administrated by intraperitoneal injection. Animals were sacrificed at different intervals after the treatment. The MNU-induced apoptosis was revealed by immunohistochemical and conventional staining. Quantitative analysis was carried out to evaluate the impacts of MNU on photoreceptors and other retinal neurons.
At 40mg/kg, MNU had little effect on photoreceptors and other retinal neurons. However, as the dosage increased to 80mg/kg, a progressive loss of photoreceptors was observed. Two to three layers of somas in the outer nuclear layer (ONL) were identifiable at five days but the ONL was absent seven days after the treatment. Consequently, the thickness of retina was reduced to approximately 70% of normal. In addition, minor changes in the inner nuclear layer (INL) were also observed. However, ganglion cell layer appeared to be morphologically intact.
The present result suggests that, at 80mg/kg, MNU completely removed photoreceptors in cat retina. Thus, it may offer an alternative way of producing an acute photoreceptor degeneration animal model in large mammals.
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