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Updated: Jul 4, 2026

Multifocal Electroretinograms
Published on: December 4, 2011
Porcine global flash multifocal electroretinogram: possible mechanisms for the glaucomatous changes in contrast
Patrick H W Chu1, Henry H L Chan1, Yiu-Fai Ng1
1Laboratory of Experimental Optometry (Neuroscience), School of Optometry, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China.
Purpose:
The aim of this study was to obtain a better understanding of the cellular contributions to the porcine global flash mfERG by using a pharmacologic dissection method, together with the method using variation of stimulus contrast which has been used to demonstrate mfERG changes in human glaucoma.
Methods:
Global flash mfERGs with different stimulus-contrast settings (99%, 65%, 49% or 29%) were recorded from 14 eyes of ten 6-week-old Yorkshire pigs in control conditions and after suppression of inner retinal responses with inhalation of isoflurance (ISO), and injections of tetrodotoxin (TTX) and N-methyl-d-aspartic acid (NMDA). ON- and OFF-pathway responses were isolated by injection of 2-amino-4-phosphonobutyric acid (APB) and cis-2,3-piperidinedicarboylic acid (PDA).
Results:
The porcine global flash mfERG consisted of an early direct component (DC) and a late induced component (IC). ISO and TTX removed inner retinal contributions to the IC; NMDA application further abolished the oscillatory wavelets in the DC and removed the residual IC waveform. The inner retina contributed regular oscillation-like wavelets (W1, W2 and W3) to the DC and shaped the IC. After removing the inner retinal contributions, the porcine global flash mfERG waveform becomes comparable to that obtained with conventional mfERG stimulation. The remaining waveform (smoothed DC) was mainly contributed by the ON- and OFF-bipolar cells as revealed after APB or PDA injection. Photoreceptors contributed a small signal to the leading edge of N1. The characteristic of contrast response function of DC was demonstrated to be contributed by the inner retinal oscillation-like wavelets.
Conclusion:
We believe that the DC of the porcine global flash mfERG is mainly composed of contributions from photoreceptors, and ON- and OFF-bipolar cells, where inner retinal activity partially shaped the DC with superimposed regular wavelets. However, the IC is dominated by inner retinal activity. The contrast response functions of DC consisted of both outer retinal response and oscillation-like wavelets of the inner retinal response. Both contain different characteristics during contrast modulation of the stimulus, where the changes of W2 of the inner retinal response seem independent of contrast modulation. The DC contrast response feature depends mainly on the relative contribution of inner retinal activities; the loss of inner retinal cells may alter the DC contrast response function, making it tend toward linearity.
Insights
This study dissects the cellular origins of the porcine global flash multifocal electroretinogram (mfERG). Inner retinal activity shapes the direct component (DC) and dominates the induced component (IC), offering insights into retinal disease mechanisms.
Area of Science:
- Ophthalmology
- Neuroscience
- Retinal Physiology
Background:
- The multifocal electroretinogram (mfERG) is crucial for assessing retinal function, particularly in conditions like glaucoma.
- Understanding the cellular contributions to the global flash mfERG in animal models is essential for interpreting human studies.
- Pharmacologic dissection offers a method to differentiate neural pathway contributions to retinal electrical responses.
Purpose of the Study:
- To elucidate the cellular origins of the porcine global flash mfERG using pharmacologic agents and contrast variation.
- To differentiate the roles of the inner and outer retina in generating mfERG components.
- To investigate the impact of stimulus contrast on mfERG waveform characteristics.
Main Methods:
- Global flash mfERGs were recorded from Yorkshire pigs under varying stimulus contrast conditions (99%–29%).
- Pharmacologic agents, including isoflurane (ISO), tetrodotoxin (TTX), and N-methyl-d-aspartic acid (NMDA), were used to suppress inner retinal activity.
- Specific pathway responses were isolated using 2-amino-4-phosphonobutyric acid (APB) and cis-2,3-piperidinedicarboylic acid (PDA) to isolate ON- and OFF-pathway signals.
Main Results:
- The porcine mfERG comprises a direct component (DC) and an induced component (IC).
- Inner retinal activity, including oscillatory wavelets (W1-W3), contributes significantly to the DC and shapes the IC.
- After pharmacologic isolation of inner retinal contributions, the mfERG waveform resembles conventional mfERG, with remaining signals attributed to photoreceptors and bipolar cells.
Conclusions:
- The DC of the porcine global flash mfERG is primarily generated by photoreceptors and ON/OFF-bipolar cells, modulated by inner retinal wavelets.
- The IC is predominantly driven by inner retinal activity.
- Contrast response functions are influenced by both outer retinal responses and inner retinal wavelets, with potential alterations in linearity upon loss of inner retinal cells.
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