Preservation of inner retinal responses in the aged Royal College of Surgeons rat. Evidence against glutamate excitotoxicity in photoreceptor degeneration

Abstract

Purpose: The aged Royal College of Surgeons (RCS) rat with advanced retinal degeneration loses the b-wave and shows a negative-going corneal electroretinogram (ERG) that has been attributed to loss of inner retinal function because of glutamate toxicity. The authors investigated the origin of this negative ERG and evaluated inner retinal function in late-stage RCS degeneration.

Methods: The ERG a-wave, b-wave, and scotopic threshold response (STR) were used to follow degeneration in RCS dystrophic animals between 18 and 120 days of age. Glutamate analogs were given by intravitreal injection to suppress transmission from photoreceptors to second- and third-order neurons to identify the origin of the negative ERG observed in older RCS dystrophic rats.

Results: In RCS dystrophic animals, the ERG developed normally up to day 27, but thereafter a- and b-wave sensitivity deteriorated more rapidly than the STR. By day 60, the STR threshold was elevated only 1 log unit, whereas a- and b-wave thresholds were > 2 log units higher than in controls. The STR range in dystrophic rats extended to brighter intensities previously dominated by the b-wave. Glutamate analogs eliminated the STR as well as the entire negative-going ERG in older dystrophic rats.

Conclusions: The negative ERG in older RCS dystrophic rats originates in the inner retina and not from photoreceptors. Inner retinal signaling remains sensitive despite major photoreceptors loss in RCS rats, consistent with previous psychophysical findings. The b-wave may not be as useful as the STR in detecting loss of quantal catch in degenerating retinas. The ERG provides no evidence of glutamate excitotoxic damage to neurons postsynaptic to degenerating RCS photoreceptors.