Rod and cone contributions to the a‐wave of the electroretinogram of the macaque

Abstract

The electroretinogram (ERG) of anaesthetised dark‐adapted macaque monkeys was recorded in response to ganzfeld stimulation and rod‐ and cone‐driven receptoral and postreceptoral components were separated and modelled. The test stimuli were brief (< 4.1 ms) flashes. The cone‐driven component was isolated by delivering the stimulus shortly after a rod‐saturating background had been extinguished. The rod‐driven component was derived by subtracting the cone‐driven component from the mixed rod–cone ERG. The initial part of the leading edge of the rod‐driven a‐wave scaled linearly with stimulus energy when energy was sufficiently low and, for times less than about 12 ms after the stimulus, it was well described by a linear model incorporating a distributed delay and three cascaded low‐pass filter elements. Addition of a simple static saturating non‐linearity with a characteristic intermediate between a hyperbolic and an exponential function was sufficient to extend application of the model to most of the leading edge of the saturated responses to high energy stimuli. It was not necessary to assume involvement of any other non‐linearity or that any significant low‐pass filter followed the non‐linear stage of the model. A negative inner‐retinal component contributed to the later part of the rod‐driven a‐wave. After suppressing this component by blocking ionotropic glutamate receptors, the entire a‐wave up to the time of the first zero‐crossing scaled with stimulus energy and was well described by summing the response of the rod model with that of a model describing the leading edge of the rod‐bipolar cell response. The negative inner‐retinal component essentially cancelled the early part of the rod‐bipolar cell component and, for stimuli of moderate energy, made it appear that the photoreceptor current was the only significant component of the leading edge of the a‐wave. The leading edge of the cone‐driven a‐wave included a slow phase that continued up to the peak, and was reduced in amplitude either by a rod‐suppressing background or by the glutamate analogue, cis‐piperidine‐2,3‐dicarboxylic acid (PDA). Thus the slow phase represents a postreceptoral component present in addition to a fast component of the a‐wave generated by the cones themselves. At high stimulus energies, it appeared less than 5 ms after the stimulus. The leading edge of the cone‐driven a‐wave was adequately modelled as the sum of the output of a cone photoreceptor model similar to that for rods and a postreceptoral signal obtained by a single integration of the cone output. In addition, the output of the static non‐linear stage in the cone model was subject to a low‐pass filter with a time constant of no more than 1 ms. In conclusion, postreceptoral components must be taken into account when interpreting the leading edge of the rod‐ and cone‐driven a‐waves of the dark‐adapted ERG.

Postreceptoral contributions to the light-adapted ERG of mice lacking b-waves

“…4A shows that PDA began to alter the leading edge of the awave around 8-10 ms after the flash, consistent with other mouse studies from this lab (Maeda et al, 2003;Ohtoshi et al, 2004). In macaques effects of intravitreal PDA injection can be seen as early as 5 ms after a brief flash (Robson et al, 2003). In Figs. 2, 4 and 6 in the present study it can be seen that the negative potential that PDA eliminated peaked around 50 ms after the flash in Nob mice (slightly earlier in Control APB mice).…”

“…As previously described for primates, as well as for mice, Off pathway activity contributes to the leading edge of the a-wave under light-adapted conditions quite early in the response (Bush and Sieving, 1994;Robson et al, 2003;Maeda et al, 2003;Ohtoshi et al, 2004;Sharma et al, 2005). In the present study Fig.…”

Retinitis Pigmentosa in Northern Sweden - From Gene to Treatment

“…As the mixed awave shows normalized responses in the majority of the young BD cases examined, and the leading edge of the a-wave mainly represents a light-evoked hyperpolarization of the photoreceptors (Brown, 1968;Jamison et al, 2001;Robson et al, 2003;Tomita, 1965), these data suggest an additional, extremely slow regeneration of photopigments occurring even after 10 h DA. No obvious recovery of the cone b-wave is noted after the extremely prolonged DA (24 h); therefore, a relatively early damage to the cone system in BD patients cannot be excluded.…”

Electroretinogram Assessment of Dark Adaptation and Rod Phototransduction from the Central Retina of Japanese Macaques with Dominantly Inherited Drusen

“…Rod isolated ERG a-waves ( Figure 5C) were then obtained by subtracting a dark-adapted cone-isolated ERGs ( Figure 5B) from the mixed rod/cone responses ( Figure 5A). Rod ERG a-wave amplitude was measured at 6 millisecond post flash ( Figure 5C: vertical dotted line) to avoid contamination by post-receptoral components that may be present at the a-wave peak (Robson et al, 2003). Figure 5D shows the recovery of rodisolated full-field rod ERG a-wave amplitude plotted as a function of post-bleach time.…”

“…The "leading edge" of the ERG a-wave for each flash intensity was determined to be all points with amplitude less than 80% of the a-wave peak. The 80% value was chosen to avoid the influence of the post-receptoral components that contribute to the awave near its peak (Robson et al, 2003). During fitting, Rmax P3 was fixed at the maximal awave amplitude obtained and S and t d were varied.…”