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S.G. Coupland, D. Petrin, A. Baker, J. Brousseau, C. Tsilfidis; Determining an Ideal Dosage of N-methyl-N-nitrosourea to Quickly Screen for Neuroprotective Compounds that can Prevent Retinal Degeneration . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1876.
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Purpose: To determine an optimal dosage of MNU that would be used to screen for neuroprotective compounds that could be used in treating genetic retinal dystrophies in animal models. Methods: Twenty male Sprague-Dawley rats at five weeks of age were divided into five groups of four animals. Flash ERGs were recorded in dark-adapted rats over 11 step scotopic-photopic range (-3.0 to 1.4 log cd-s/m2) prior to MNU treatment. Groups one through five were given intraperitoneal injections of 20, 30, 40, 50 and 60 mg/kg MNU, respectively. Rats then underwent the same electroretinogram (ERG) protocol at 24h, 72h and one-week post-MNU injection. ERGs at all intensities were scored, averaged and the latencies and amplitudes were imported into Excel spreadsheets. The b-wave amplitudes were then imported into Sigma Plot 7.0 where a Naka-Rushton equation was used to fit the response versus luminance. Results: Using an analysis of variance (ANOVA) test, no significant difference in Rmax was found between all groups at pre-treatment baseline. There was no significant difference in Rmaxat the 72h and 1-week time points, indicating that maximal damage to the retina occured by 72 hours. No appreciable reduction in Rmax was observed in the 20 and 30 mg/kg dose groups. However, we found that a significant reduction in Rmax at 72h occured at the 40 mg/kg dose and the magnitude of this Rmax reduction increased at 50 and 60 mg/kg of MNU. Conclusions: These findings suggest that a 40 mg/kg dose of MNU is sufficient to screen for neuroprotective effect of compounds which can prevent retinal degeneration from occurring. In addition, it is suggested that MNU produced maximal change in electroretinal function occurs by 72 hours.
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