Rod Phototransduction in Retinitis Pigmentosa: Estimation and Interpretation of Parameters Derived from the Rod A-wave

Purpose: Relationships between the Lamb and Pugh model of transduction in single rod photoreceptors and the parameters derived from human rod a-waves are examined to evaluate transduction abnormalities in retinitis pigmentosa (RP) and cone-rod dystrophy (CRD).

Methods: ERGs were obtained from 15 patients, 11 with RP and 4 with CRD, and from 15 normal subjects. Rod-only responses were derived from responses to blue (W47B) flashes over a wide range of flash energies by computer-subtracting estimates of the cone contribution. A model of the rod's response was fitted to the a-waves of the rod-only responses as well as to the responses to the blue flashes by estimating three parameters-sensitivity (S), delay (td), and maximum response (RmP3). To assess the limits of the cone contributions to the parameters of the model, ERGs were obtained from two of the patients, two normal subjects, and three additional patients with nondetectable rod responses using white flashes.

Results: All patients had significantly decreased values of RmP3, and eight had significantly decreased values of S compared to the control subjects. The values of the parameters estimated from the responses to the blue flashes were reasonably similar to those for the rod-only responses except in patients with nondetectable rod signals. For the white flashes, the estimate of S was considerably larger and the fit of the model noticeably poorer.

Conclusions: The authors reached two conclusions. First, some forms of RP and CRD alter the activation stages of transduction. Transduction appears normal in other patients, despite extensive receptor damage as indicated by markedly reduced RmP3 values. Second, the cone contribution to a blue flash only affects the estimate of the key parameters in patients in whom the rod component is minimal. The cone contribution to a white flash contaminates the fit and the estimate of the parameters in all patients and normal subjects.