Autosomal dominant rod-cone dysplasia in the Rdy cat : 2. Electrophysiological findings

Abstract

Electroretinography was performed on cats affected with autosomal dominant rod-cone dysplasia (gene symbol Rdy). In normal kittens it was found that retinal sensitivity increased and rod thresholds decreased as the animals matured. Electroretinogram (ERG) amplitudes were mature by 4·5 weeks and adult timing was attained by 6 weeks of age, consistent with the findings of other workers. In Rdy-affected heterozygous kittens the ERG was absent or barely recordable using conventional corneal contact lens electrodes. However, the enhanced sensitivity of an intravitreal needle electrode permitted the recording of ERGs from affected kittens aged 4·5 weeks and older. The intravitreally recorded scotopic ERG in Rdy-affected kittens was a very low amplitude, largely negative response with prolonged a- and b-wave times-to-peak (two to threefold longer than in comparable recordings from an age-matched normal kitten). The b-wave lacked oscillatory potentials and was relatively small so that the ERG was a-wave dominated. This was attributed to delayed and defective synaptogenesis in the outer plexiform layer of dystrophic retinas. In contrast to normal kittens, the b-wave threshold was higher than that of the a-wave in affected kittens. Photopic responses were unrecordable. The intravitreal ERG was barely recordable in a 5-month-old Rdy-affected cat and was apparently extinguished by 7 months of age. In vitro electroretinography permitted a comparison of the photoreceptor responses (fast PIII) from the isolated retinas of 6-week-old control and Rdy-affected heterozygous kittens. Maximum fast PIII amplitudes were reduced by about 75% in affected retinas compared with age-matched normal retinas ( P < 0·005). The mean fast PIII time-to-peak, at maximum light intensity, in Rdy-affected retinas was prolonged by about 15 msec and was approximately twofold longer than the time-to-peak of normal retinas ( P < 0·005). The fast PIII response threshold (light intensity at 5 μV response) was increased by 1·0 log unit in affected retinas, and there was also a 0·94 log unit reduction in photoreceptor sensitivity (σ), indicated by the shift of the amplitude-response curve ( V-log I function) towards higher light intensities and a corresponding increase in semi-saturation luminance. These findings correlate well with the paucity of photoreceptor outer segment material, and therefore reduced rhodopsin content, seen histologically in affected retinas. The altered slope of the fast PIII V-log I function of Rdy-affected retinas indicated a smaller increase in relative fast PIII amplitude per log unit light intensity in dystrophic photoreceptors. The fast PIII time-to-peak vs. light intensity curve ( T-log I function) of Rdy-affected retinas had a steeper slope with relatively greater prolongations in time-to-peak at lower luminances compared with normal retinas ( P < 0·025). These changes in temporal characteristics may be explained either by severe disorganization of photoreceptor outer segments or by altered phototransduction kinetics.