Post-receptoral rod and cone abnormalities in retinitis pigmentosa caused by rhodopsin gene mutations

Purpose. To determine the extent of inner retinal dysfunction in primary rod outer segment diseases. Methods. Fifteen families with autosomal dominant retinitis pigmentosa (RP) and rhodopsin gene mutations were studied with rod- and cone-isolated electroretinograms (ERGs) over a wide stimulus range. Rod and cone photoresponses were quantified using a biochemically based model of transduction fitted to the a-wave data. Naka-Rushton functions were fitted to rod b-wave amplitudes, and the amplitude and timing of the post-receptoral component of the cone ERG analyzed. Results. Rod photoresponses had reduced maximum amplitude with normal sensitivity. The waveforms of rod-isolated b-waves elicited with high stimulus energies indicated different degrees of rod inner retinal involvement. Rod b-wave logK abnormalities were not explained by photoresponse sensitivity changes. Cone photoresponses could be normal even in the presence of delays in cone flicker timing. Abnormal cone photoresponses were accompanied by greater delays in timing, which were unexplained by reductions in cone photoreceptor sensitivity. The extent of cone inner retinal dysfunction was directly related to the loss of rod photoresponse amplitude. Conclusions. These primary rod outer segment diseases can show disproportionate rod post-receptoral dysfunction. The secondary cone disease may first be detectable at post-receptoral sites before there is cone outer segment loss. These results may be the functional correlate of abnormal photoreceptor processes found in the inner retina of RP donor eyes (Li, Kljavin & Milam; J Neurosci; 15:5429-5438, 1995).