Modelling the initial phase of the human rod photoreceptor response to the onset of steady illumination

Abstract

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.

Electrical responses from human retinal cone pathways associate with a common genetic polymorphism implicated in myopia

“…In standard testing, although dark-adapted responses are largely rod-driven, responses to the standard and bright flashes (DA 3 and DA 10, respectively) contain significant contributions from stimulation of cone photoreceptors. The rod- and cone-mediated contributions to the ERG a-wave response to flashes delivered in the dark can be parsed by delivering identical flashes in the presence of a dim blue background (calculated to saturate the rods but minimally desensitize the cones) ( 17 , 18 ). This yields dark-adapted cone-mediated responses; subtraction of these from responses to the same flashes in the dark yields an estimated dark-adapted rod photoreceptor response.…”

“…The responses to flashes delivered on the dim blue rod-saturating background reflected the dark-adapted cone-driven response. Mathematical subtraction of these responses (cone-driven) from those to identical flashes delivered in the dark (rod- and cone-driven) yielded the isolated dark-adapted rod-driven response (i.e., with the cone-driven components removed) ( 18 ).…”

Negative electroretinograms: genetic and acquired causes, diagnostic approaches and physiological insights

“…Several previous studies have applied mathematical models of rod photocurrent responses [ 91 ] to fit the ERG [ 92 – 94 ], and have assumed that the bright flash dark-adapted a-wave trough, and the immediate recovery following the trough, is due to the intrusion of depolarising currents in ON bipolar cells. Loss of ON bipolar cell depolarisation would then be expected to result in an increased a-wave amplitude.…”

Modeling and simulation of phototransduction cascade in vertebrate rod photoreceptors

“…When the molecules of rod photoreceptors, rhodopsin, absorb photons, a cascade of reactions are triggered [10, 13]. This eventually results in the decline of intracellular cGMP concentration and closure of cGMP gated Na + /Ca 2+ ion channels in plasma membrane of rods, and leads to changes of electrical current and voltage [17]. The electrical current or voltage from the photoreceptors is an important part of electroretinogram (ERG), which is the summation of a few components of extracellular currents from different cells [13, 25, 28].…”

“…In literature, there are many efforts on modeling and simulation of phototransduction cascade in rods and ERG generation [6, 9, 11, 12, 16, 17, 21, 26, 27]. A recent review on modeling the retina in health, development and disease was well conducted by Roberts et al [24].…”