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P.J. DeMarco, M.A. McCall; Functional Consequences of Delayed Photoreceptor Ablation in Transgenic Mice . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1869.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To characterize the functional changes in the retina of a transgenic mouse line (rdtalate) with delayed rod photoreceptor degeneration. Methods: We have previously reported the effects of transgene-induced rod photoreceptor degeneration in rdta mice, which express an attenuated diphtheria toxin gene under the control of a rhodopsin promoter. In a third line of these mice, the phenotype is delayed with rod ablation evident after 42 days of age. Once begun, rod degeneration follows a time course similar to the other two lines and appears to be complete by 60 days of age. This delay in transgene expression in the rdtalate mice allows both the rod and cone photoreceptors to complete normal development before the onset of degeneration. To characterize retinal function in these animals, the full-field light-adapted ERG was recorded from anesthetized mice using a DTL fiber electrode. A xenon arc lamp light source was used to present broad-band light flashes, 10ms in duration, with a 1 sec inter-stimulus interval. Light-adapted mice were positioned in the recording apparatus, and then the room lights were extinguished to begin dark-adaptation. A constant intensity flash was used to elicit the ERG at 1 min intervals for 15 min, and then at 5 min intervals up to 40 min. Thirty responses were averaged at each time point. Normal mice (C57B6/J) were used as age-similar controls. Dark-adaptation functions were constructed by plotting the ERG response as a function of time in the dark. Results: In normal mice, the dark-adaptation curve was described by a two-limbed function, characteristic of the rod-cone transition that occurs during dark-adaptation. Dark-adaptation in rdtalate mice was similar to controls up to about 45 days of age. At that age, a change in the dark-adaptation curves becomes evident with a shallower scotopic limb. By about 70 days, the dark-adaptation curves consist of only a cone limb. After 120 days there is little in the way of an ERG response, suggesting that cone function eventually becomes compromised. Conclusions: These data suggest that, during a window around 50 days of age, the retinal response of rdtalate mice is dominated by cone photoreceptors. The electrophysiology is consistent with the time course of the anatomical degeneration of the rods in rdtalate mice, which is complete around the same age. These data suggest that rdtalate mice may serve as a model to study both the functional consequences of rod dystrophies, and within a certain time frame, the cone pathways in isolation.
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