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James D Akula, Lucia Ambrosio, Fiona Howard, Ronald M Hansen, Anne B Fulton; Extracting the ON and OFF Contributions to the Full-Field Photopic Flash Electroretinogram Using Serial Logistic Growth Curves. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4243.
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© ARVO (1962-2015); The Authors (2016-present)
An “instantaneous” flash of light simultaneously activates both depolarizing (ON) and hyperpolarizing (OFF) retinal responses that respectively “push” and “pull” the amplitude of the electroretinogram (ERG). Like many physiological responses, the stimulus/response (SR) relationship of ON-responses demonstrate logistic growth, manifested in the saturating, scotopic b-wave. However, under photopic conditions, OFF responses importantly shape the b-wave SR function, leading to a “photopic hill” (a peak followed by a non-zero plateau). These OFF responses, too, presumably follow logistic growth. We evaluated the principle that the sum of respective, logistic SR functions could describe the photopic ERG at arbitrary times after the flash and consequently be used to extract putative ON and OFF contributions to the ERG.
We studied extant photopic ERG responses to a range of stimulus intensities (-0.6–2.1 log cd.s.m-2) obtained in healthy Adult (n=32), 10-week-old Infant (n=29), congenital stationary night blindness (CSNB, n=8), and X-linked juvenile retinoschisis (XJR, n=9) subjects. After applying a bandstop filter (60–235 Hz) to remove the oscillatory potentials, we used a novel fitting routine to optimize a sum of two-parameter (amplitude, sensitivity) logistic curves to SR data at 2 ms intervals following the flash (0–50 ms). We then derived model ON and OFF responses at arbitrary intensities by replotting the serial respective logistic curves. Differences in ON and OFF sensitivity and amplitude among the groups were evaluated using repeated measures analysis of variance after recasting all variables as the log difference from Adult (ΔLogNormal).
In Adult ERGs, the putative ON and OFF pathways were each well-described by skewed distributions (e.g. Weibull functions) with similar (though opposite polarity) amplitudes and respectively longer and shorter implicit times. Infant, CSNB, and XJR subjects who, notably, lacked photopic hills, showed respectively increasingly severe, highly significant, ON pathway deficits.
This novel modeling procedure makes possible the derivation of the ON and OFF pathway contributions to the intact ERG and may produce parameters with far more direct physiological relevance than those of currently available models.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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