Sites of disease action in a retinal dystrophy with supernormal and delayed rod electroretinogramb-waves

Delayed rod ERG b-waves in patients with an unusual retinal dystrophy have been attributed by some to an abnormality in receptor cGMP activity. Here the sites of disease action are studied by analyzing rod and cone ERGs using new analytical methods and a wide range of stimulus intensities. Consistent with previous reports, the five patients studied showed rod b-waves that were normal or supernormal in amplitude in response to intense flashes, but smaller than normal and markedly delayed in response to weaker flashes. The cone ERGs, recorded to 29 Hz flicker and to flashes upon a background, were smaller than normal and also showed delays. Models of phototransduction fitted to rod and cone a-waves indicated that the delays in the rod and cone b-waves were not due to the speed or amplification of the transduction process. An analysis of the derived inner nuclear layer (INL) response suggests that the sites of disease action are beyond the outer segment and involve a delay in the activation of INL activity.