Purpose: At lower stimulus intensities, the amplitude of the photopic flash ERG b-wave increases with increasing stimulus intensities, but then plateaus and decreases at higher stimulus intensities (the "photopic hill"). The purpose of this study was to determine the mechanism underlying this unusual phenomenon.
Methods: Five adult monkeys (Macaca mulatta and M. fascicularis) were studied. Stimuli were obtained from xenon strobe flashes, and the intensity was reduced by neutral-density filters in 0.4-log unit steps. N-methyl-D-aspartic acid and tetrodotoxin citrate (NMDA+TTX) were used to suppress inner retinal activities and L-2 amino-4-phosphonobutyric acid (APB) and cis-2,3 piperidine dicarboxylic acid (PDA) to block postreceptoral ON- and OFF-pathway activities. The postsynaptic ON- and OFF-components were isolated by subtracting the postdrug ERGs from the predrug ERGs.
Results: The intensity-response curve of the photopic b-wave obtained after the intravitreal injection of TTX+NMDA had the same shape as a photopic hill, suggesting that the contribution from the inner retinal neurons to the photopic hill is not significant. At low and intermediate intensities, the photopic b-wave was mainly shaped by the overlapping of two positive peaks from the ON- and OFF-components. However, the amplitude of the positive peak from the ON-component became smaller and broader at higher stimulus intensities. In addition, the timing of the positive peak of the OFF-component was gradually delayed with increasing intensities. After APB+PDA, the remaining cone photoreceptor component contributed only to the negative a-wave at all stimulus intensities.
Conclusions: The photopic hill in the primate ERG results mainly from two factors: the reduction of the ON-component amplitude at higher intensities and the delay in the positive peak of the OFF-component at higher intensities.