The ionic fluxes described above give rise to radial currents that underlie various components of the electroretinogram (ERG), a light-evoked transretinal potential widely used as a noninvasive, objective test of retinal function in the differential diagnosis of visual disorders (cf. Goodman and Ripps, 1960; Ripps, 1982; Hood and Birch, 1990; Berson, 1993). Whether recorded across the retina, i.e., between electrodes in the vitreous and at the basal surface of the RPE, or with a contact lens electrode on the cornea of the intact eye, the ERG response evoked by the onset of illumination consists primarily of three readily detectable components: the a-, b-, and c-waves. The variation in response polarity and time course indicate that this complex waveform reflects the summation of potentials arising from different sources. Each component is itself a composite derived from more than one cellular source.
There has long been interest in the cellular origins of the ERG potentials and the mechanisms by which they are generated. Investigators have attempted to address these questions with intracellular recordings, pharmacological intervention, and current-source density (CSD) analysis. CSD provides a means for determining the "sources" and "sinks" of extracellular current flow based on depth recordings of tissue resistivity and intraretinal voltage in response to photic stimulation (cf. Nicholson and Freeman, 1975; Xu and Karwoski, 1994a). The results have shown that, for the most part, the potentials that underlie the ERG derive from the light-evoked ionic currents of radially oriented retinal neurons, Müller cells, and pigment epithelial cells. An oversimplified scheme depicting how several of these cell types can contribute to a response envelope that resembles the ERG is illustrated in Fig. 5.16, and described more fully in the following sections.
The initial response to photic stimulation is a rapid cornea-negative deflection referred to as the a-wave, or the "fast PIII" component of the ERG. By recording the light-induced voltage between two microelectrodes positioned near the distal and proximal ends of the photoreceptors in the rat retina, Penn and Hagins (1969) showed that the leading edge of the a-wave reflects the change in radial current flow that results from closure of the Na+ channels in the outer segment membranes; i.e., the response is essentially a reduction of the "dark current" and a reversal of the source-sink current paths (Fig. 5.17). Although potassium ions are not a significant factor in the generation of the a-wave, it is important to recall that the ionic
Figure 5.16. Schematic representation of several of the components that summate to give rise to the a, b, and owaves ofthe trans-retinal ERG (bold continuous line). Light-evoked radial currents are generated by the photoreceptors, bipolar cells, the retinal pigment epithelium, and the Müller cells. The leading edge of the a-wave is dominated by the hyperpolarizing receptor potential (RP), whereas the rapidly rising transient phase ofthe b-wave reflects activation of depolarizing ON bipolar cells (DB) and the K+-mediated response of Müller cells. The slowly rising c-wave receives contributions of opposite polarity from the retinal pigment epithelium (RPE) and the Müller cell (slow PIII). In this simplified drawing, contributions from cells of the inner retina (e.g., oscillatory potentials) and the response to light offset are omitted (Ripps and Witkovsky, 1985). (Copyright 1985 Else-
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