Light adaptation of human rod receptors: the leading edge of the human< i> a-wave and models of rod receptor activity (original) (raw)
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Rod transduction parameters from the a wave of local receptor populations
1995
The analysis of electroretinogram a waves from locally stimulated populations of rods is complicated by the presence of scattered light within the eye. Scattered-light and cone contributions can be assessed after brief flashes of light designed to saturate only rods in the locally stimulated area. Subtracting the scattered-light and the cone responses from the local electroretinogram gives a pure rod a wave that can be fitted with models of photoreceptor activity. We demonstrate the feasibility of this technique by recording local rod a waves from a group of five normal subjects and by fitting the a waves with the rod model to derive transduction parameters. The local rod a waves are compared with expected responses derived from simulations in which the response of the entire retina to heterogeneous illumination is mimicked.
2012
The initial time course of the change in photoreceptor outer segment membrane conductance in response to light flashes has been modelled using biochemical analysis of phototransduction, and the model has been successfully applied to a range of in vitro recordings and has also been shown to provide a good fit to the leading edge of the electroretinogram a-wave recorded in vivo. We investigated whether a simple modification of the model's equation would predict responses to the onset of steady illumination and tested this against electroretinogram recordings. Scotopic electroretinograms were recorded from three normal human subjects, using conductive fibre electrodes, in response to light flashes (0.30-740 scotopic cd m(-2) s) and to the onset of steady light (11-1,900 scotopic cd m(-2)). Subjects' pupils were dilated pharmacologically. The standard form of the model was applied to flash responses, as in previous studies, to obtain values for the three parameters: maximal response amplitude r (max), sensitivity S and effective delay time t (eff). A new "step response" equation was derived, and this equation provided a good fit to rod responses to steps of light using the same parameter values as for the flash responses. The results support the applicability of the model to the leading edge of electroretinogram responses: in each subject, the model could be used to fit responses both to flashes of light and to the onset of backgrounds with a single set of parameter values.
Vision Research, 1996
A quantitative description of the activation reactions in the cGMP phototransduction cascade has been recently developed [Lamb & Pugh (1992).Journalo~Physiobgy, 449, 719-758]. When applied to the human electroretinogram a-wave, the widely used simplified form of this model provides a good description of all waveforms except those elicited with very high energy stimuli. The basis for these misfits at high energies is explored in the current study and an alternative model of phototransduction is derived that retains the quantitative aspects but avoids certain simplifying assumptions previously made. The new model describes well both rod-and cone-isolated a-waves over a large range of stimulus energies extending up to those that cause significant bleaching. To facilitate clinical application of this methodology, a short test protocol is developed and normal data for rod and cone transduction parameters are provided over a wide age range. In the sample of normal subjects studied, maximum amplitude of rod and cone a-waves and sensitivity of the cone awave do not change with age. An age-related decline in rod a-wave sensitivity is present and it is greater than that expected from pre-retinal absorptionalone.
A study of the human rod and cone electroretinogram a-wave component
Journal of Statistical Mechanics: Theory and Experiment, 2009
The study of the electrical response of the retina to a luminous stimulus is one of the main fields of research in ocular electrophysiology. The features of the first component (a-wave) of the retinal response reflect the functional integrity of the two populations of photoreceptors: rods and cones. We fit the a-wave for pathological subjects with functions that account for possible mechanisms governing the kinetics of the photoreceptors. The paper extends a previous analysis, carried out for normal subjects, in which both populations are active, to patients affected by two particular diseases that reduce the working populations to only one. The pathologies investigated are Achromatopsia, a cone disease, and Congenital Stationary Night Blindness, a rod problem. We present evidence that the analysis of a pathological a-wave can be employed to quantitatively measure either cone or rod activities and to test hypotheses about their responses. The results show that the photoreceptoral responses differ in the two cases and functions implying a different number of photocascade stages are necessary to achieve a correct modeling of the early phototransduction process. Numerical values of the parameters characterizing the best-fit functions are given and discussed.
Visual transduction in human rod photoreceptors
The Journal of physiology, 1993
1. Photocurrents were recorded with suction electrodes from rod photoreceptors of seven humans. 2. Brief flashes of light evoked transient outward currents of up to 20 pA. With increasing light intensity the peak response amplitude increased along an exponential saturation function. A half-saturating peak response was evoked by approximately sixty-five photoisomerizations. 3. Responses to brief dim flashes rose to a peak in about 200 ms. The waveform was roughly like the impulse response of a series of four to five low-pass filters. 4. The rising phases of the responses to flashes of increasing strength were found to fit with a biochemical model of phototransduction with an 'effective delay time' and 'characteristic time' of about 2 and 800 ms, respectively. 5. Spectral sensitivities were obtained over a wavelength range from 380 to 760 nm. The action spectrum, which peaked at 495 nm, followed the template described for photoreceptors in the macaque retina. Variation...
The rod-driven a-wave of the dark-adapted mammalian electroretinogram
Progress in retinal and eye research, 2014
The a-wave of the electroretinogram (ERG) reflects the response of photoreceptors to light, but what determines the exact waveform of the recorded voltage is not entirely understood. We have now simulated the trans-retinal voltage generated by the photocurrent of dark-adapted mammalian rods, using an electrical model based on the in vitro measurements of Hagins et al. (1970) and Arden (1976) in rat retinas. Our simulations indicate that in addition to the voltage produced by extracellular flow of photocurrent from rod outer to inner segments, a substantial fraction of the recorded a-wave is generated by current that flows in the outer nuclear layer (ONL) to hyperpolarize the rod axon and synaptic terminal. This current includes a transient capacitive component that contributes an initial negative "nose" to the trans-retinal voltage when the stimulus is strong. Recordings in various species of the a-wave, including the peak and initial recovery towards the baseline, are con...
Journal of the Optical Society of America, 1996
Electroretinographic data obtained from human subjects show that bright test flashes of increasing intensity induce progressively longer periods of apparent saturation of the rod-mediated electroretinogram (ERG) a wave. A prominent feature of the saturation function [the function that relates the saturation period T with the natural logarithm of flash intensity (ln I f ] is its two-branched character. At relatively low flash intensities (I f below ϳ4 3 10 4 scotopic troland second), T increases approximately in proportion to ln I f with a slope [DT͞D͑ln I f ͒] of Ӎ 0.3 s. At higher flash intensities, a different linear relation prevails, in which [DT͞D͑ln I f ͒] is Ӎ2.3 s [Invest. Ophthalmol. Vis. Sci. 36, 1603 (1995)]. Based on a model for photocurrent recovery in isolated single rods [Vis. Neurosci. 8, 9 (1992)], it was suggested that the upper-branch slope of Ӎ2.3 s represents t R ء , the lifetime of photoactivated rhodopsin (R ء). Here we show that a modified version of this model provides an explanation for the lower branch of the a-wave saturation function. In this model, t E ء is the exponential lifetime of an activated species (E ء) within the transducin or guanosine 3 0 , 5 0-cyclic monophosphate (cGMP) phosphodiesterase stages of rod phototransduction; the generation of E ء by a single R ء occurs within temporally defined, elemental domains of disk membrane; and E x , the immediate product of E ء deactivation, is converted only slowly (time constant t Ex) to E, the form susceptible to reactivation by R ء. The model predicts that the decay of flash-activated cGMP phosphodiesterase (PDE*) is largely independent of the deactivation kinetics of R ء at early postflash times (i.e., at times preceding or comparable with the lifetime t E ء) and that the lower-branch slope (Ӎ0.3 s) of the a-wave saturation function represents t E ء. The predicted early-stage independence of PDE* decay and R ء deactivation furthermore suggests a basis for the relative constancy of the single-photon response observed in studies of isolated rods. Numerical evaluation of the model yields a value of Ӎ 6.7 s for the time constant t Ex .
Experimental Eye Research, 2019
The canine species has dichromatic color vision comprising short-wavelength (S-) and long/medium (L/M-) wavelength-sensitive cones with peak spectral sensitivity of 429-435 nm and 555 nm respectively. Although differentiation of rod-and cone-mediated responses by electroretinogram (ERG) in dogs is commonly performed, and standards have been developed based on standards for human observers, methods to differentiate Sand L/ M-cone responses in dogs have not been described. We developed flicker protocols derived from previously published rod and cone spectral sensitivities. We used a double silent substitution paradigm to isolate responses from each of the 3 photoreceptor subclasses. ERG responses were measured to sine-wave modulation of photoreceptor excitation at different temporal frequencies (between 4 and 56 Hz) and mean luminance (between 3.25 and 130 cd/m 2) on 6 different normal dogs (3 adult female, and 3 adult male beagles) and one female beagle dog with suspected hereditary congenital stationary night blindness (CSNB). Peak rod driven response amplitudes were achieved with low frequency (4 Hz, maximal range 4-12 Hz) and low mean luminance (3.25 cd/m 2). In contrast, peak L/M-cone driven response amplitudes were achieved with high frequency (32 Hz, maximal range 28-44 Hz) and high mean luminance (32.5-130 cd/m 2). Maximal Scone driven responses were obtained with low frequency stimuli (4 Hz, maximal range 4-12 Hz) and 32.5-130 cd/m 2 mean luminance. The dog with CSNB had reduced rod-and Scone driven responses, but normal/supernormal L/M cone-driven responses. We have developed methods to differentiate rod, Sand L/M-cone function in dogs using silent substitution methods. The influence of temporal frequency and mean luminance on the ERGs originating in each photoreceptor type can now be studied independently. Dogs and humans have similar L/M cone responses, whereas mice have significantly different L/M responses. This work will facilitate a greater understanding of canine retinal electrophysiology and will complement the study of canine models of human hereditary photoreceptor disorders.