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PJ DeMarco, MP Daniel, NS Peachey, MA McCall; Rod Photoreceptor Ablation Alters Cone Pathway Function in Transgenic Mice . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1964.
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Purpose: We characterized the effect of selective rod photoreceptor ablation on cone pathway function in a transgenic mouse. Methods: Full-field light-adapted electroretinograms (ERGs) were recorded from anesthetized mice using a conductive fiber electrode. A xenon arc lamp light source was used to present light flashes, 10-200ms in duration. Three lines of transgenic mice were created previously (1) that express an attenuated diphtheria toxin gene under the control of a rhodopsin promoter (rdta mice). In two lines, the onset of rod photoreceptor ablation coincides with rhodopsin expression. In a third line (rdtalate), a similar morphological phenotype results, however the onset of rod photoreceptor ablation is not evident until 42 days of age. Once begun, rod ablation in the rdtalate mice follows a similar time course to the rdta mice and appears to be complete by 60 days of age. This delay allows rod and cone photoreceptors to complete their normal development prior to ablation. Results: The ERG was normal in rdtalate mice up to about 50 days. At that time, a progressive change in the morphology and sensitivity of the ERG occured. At low flash intensities, the ERG was positive but less sensitive. At higher intensities, the ERG became increasingly negative and the magnitude of waveform inversion was correlated with the age of the animal. Similar ERGs were recorded from rdta mice, but at a younger age. We also compared these data to ERGs of nob mice (2), which are thought to reflect activity from only photoreceptors. While the nob ERG also is negative, its morphology is different and its amplitude is lower compared to rdtalate mice. Conclusion: These data suggest that the cone pathway may be altered by rod photoreceptor ablation in rdta mice. Because of the large amplitude of the response, we hypothesize that the modified connections between the cone photoreceptors and second-order neurons could reflect a change in the balance of cone input to hyperpolarizing and depolarizing bipolar cells. 1. McCall, et al. (1996). Exp Eye Res, 63, 35-50. 2. Pardue, et al. (1998). Invest Ophthalmol Vis Sci, 39, 2443-9.
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