The origins of the full-field flash electroretinogram b-wave

Abstract

The electroretinogram (ERG) measures the electrical activity of retinal neurons and glial cells in response to a light stimulus. Amongst other techniques, clinicians utilize the ERG to diagnose various eye diseases, including inherited conditions such as cone-rod dystrophy, rod-cone dystrophy, retinitis pigmentosa and Usher syndrome, and to assess overall retinal health. An ERG measures the scotopic and photopic systems separately and mainly consists of an a-wave and a b-wave. The other major components of the dark-adapted ERG response include the oscillatory potentials, c-wave, and d-wave. The dark-adapted a-wave is the initial corneal negative wave that arises from the outer segments of the rod and cone photoreceptors hyperpolarizing in response to a light stimulus. This is followed by the slower, positive, and prolonged b-wave, whose origins remain elusive. Despite a large body of work, there remains controversy around the mechanisms involved in the generation of the b-wave. Several hypotheses attribute the origins of the b-wave to bipolar or Müller glial cells or a dual contribution from both cell types. This review will discuss the current hypothesis for the cellular origins of the dark-adapted ERG, with a focus on the b-wave.

Keywords: Müller glia cells; a-wave; b-wave; bipolar cells; electroretinogram; potassium ions.

Figure 1

Schematic of the waveform of the three main types of Electroretinography (ERG) and their stimuli pattern. (A–C) Example traces of human responses and their respective amplitude peaks for quantification of the (A) full-field flash electroretinography (ffERG), (B) pattern electroretinography (PERG) and (C) multifocal electroretinography (mfERG). The way amplitude is measured for each waveform is represented by the solid black lines. (D) The contrast-reversing checkerboard stimuli of PERG and the (E) 61 hexagon stimuli for mfERG. (F) A representative trace array of 61 individual mfERG waveforms.

Figure 2

Schematic representation of the retina depicting which cell type contributes to which part of the in vivo scotopic electroretinogram (ERG) response recorded from a wildtype mouse (C57BL6/J). This recording was conducted via the Celeris DiagnosysLLC with a filter configuration of for the a- and b-wave the light intensity was 10 cd.s/m² with a low filter frequency cut-off of 0.125 Hz and high filter frequency cut off of 300 Hz and for the c-wave the light intensity 150 cd.s/m² was low filter frequency cut-off of 0.125 Hz and high filter frequency cut off of 100 Hz. Solid black lines represent a well-supported hypothesis, and the dashed black lines represent the possible links between the retinal cells and waveform.

Figure 3

Schematic representation and overview of the three hypotheses linked to the b-wave origin after light activation. (A) Representation of the extracellular retinal potassium (K⁺) gradient in the dark. (B) Müller glia (MG) (or K⁺) hypothesis depicting the increase of K⁺ in the distal retina contributing to the change in extracellular K⁺ leading to the generation of the b-wave. (C) MG & bipolar cell (MG-BC) hypothesis depicting the change in membrane potential of BC and the change in extracellular K⁺ via K⁺ siphoning in the MG contribute to the generation of the b-wave. (D) BC hypothesis shows that the change in membrane potential of the BC alone contributes to the generation of the b-wave. Purple lines, source/sink for the SlowPIII; Red line, source/sink for the M-wave; black line, source/sink for the b-wave; Vm, change in membrane potential; OS, Outer segment; IS, Inner Segment; ONL, Outer Nuclear Layer; OPL, Outer Plexiform Layer; INL, Inner Nuclear Layer; IPL, Inner Plexiform Layer; GCL, Ganglion Cell Layer; Blue dots, K⁺ ions; Red dots, Glutamate. The references are ¹Faber (1969), ²Dick and Miller (1978), ³Dick et al. (1985), ⁴Wen and Oakley (1990), ⁵Heckenlively and Arden (2006). ⁶Fujimoto and Tomita (1981), ⁷Newman and Odette (1984), ⁸Stockton and Slaughter (1989), ⁹Karwoski and Xu (1999), ¹⁰Gurevich and Slaughter (1993), ¹¹Tian and Slaughter (1995), and ¹²Kofuji et al. (2000).