Porcine global flash multifocal electroretinogram: possible mechanisms for the glaucomatous changes in contrast response function.
OBJECTIVE
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.


CONCLUSIONS
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.
Laboratory of Experimental Optometry (Neuroscience), School of Optometry, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China.
Patrick H W
PHW
Chu
Laboratory of Experimental Optometry (Neuroscience), School of Optometry, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China.
Henry H L
HHL
Chan
Laboratory of Experimental Optometry (Neuroscience), School of Optometry, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China.
Yiu-Fai
YF
Ng
Institute of Health and Biological Innovation and School of Optometry, Queensland University of Technology, Brisbane, Australia.
Brian
B
Brown
Laboratory of Experimental Optometry (Neuroscience), School of Optometry, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China.
Andrew W
AW
Siu
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
Brady A
BA
Beale
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
Brian C
BC
Gilger
Departments of Ophthalmology and Neurobiology, School of Medicine, Duke University, Durham, NC, USA.
Fulton
F
Wong
D000818:Animals; D015350:Contrast Sensitivity / Q000502:physiology*; D004596:Electroretinography / Q000379:methods; D005901:Glaucoma / Q000503:physiopathology* / Q000523:psychology; D010775:Photic Stimulation / Q000379:methods; D012160:Retina / Q000503:physiopathology; D034421:Sus scrofa