Leading edge of the a-wave of the electroretinogram and sodium iodate-induced age-related macular degeneration: A model.

BACKGROUND: Iron-induced oxidative stress was thought to be the reason why the a-wave amplitude of the electroretinogram (ERG) dropped when iron ions were present. It is assumed that reactive oxygen species (ROS) are generated in the presence of iron ions, and this leads to a decrease in hyperpolarization of the photoreceptor. It is known that in age-related macular degeneration (AMD), sodium iodate can induce oxidative stress, apoptosis, and retinal damage, which mimic the effects of clinical AMD. Here, the reduction of the a-wave amplitude in mice with sodium iodate-induced age-related macular degeneration is explained. METHODS: The leading edge of the a-wave is divided into voltages developed by cones and rods. The same oxidative stress model is applied here since sodium iodate causes the creation of ROS in a manner similar to that caused by iron ions, with the exception that the retina is treated as a circuit of various resistances when computing the photoresponse. Moreover, sodium iodate also leads to apoptosis and, hence, may cause misalignment in cones (not in rods) during the initial stage of apoptosis in AMD. To include the effects of apoptosis and shortening in cones and rods, we have used a factor representing the fraction of total cones and rods that are alive. To include the effect of misalignment of cones on the reduction of the a-wave amplitude, we have used the Stiles-Crawford function to calculate the number of photoisomerizations occurring in a photoreceptor misaligned at an angle θ. The results are compared with experimental data. RESULTS: In sodium iodate-treated eyes, the ROS produced can attract calcium ions in the photoreceptor, which increases the calcium influx. In the case of the cones, the inclusion of the misalignment angle in the phototransduction process helps in determining the voltage and slope of the voltage vs. time graph.The smaller the fraction of active photoreceptors, the smaller the amplitude of the a-wave. The calcium influx, misaligned photoreceptors, and total photoreceptor loss all cause the amplitude of the a-wave to decrease, and at any time from the beginning of phototransduction cascade, the calcium influx causes the slope of the a-wave to increase. CONCLUSION: The reduction in the a-wave amplitude in the eyes of sodium iodate-treated mice is attributed to oxidative stress in both cones and rods and cone misalignment, which ultimately lead to apoptosis and vision loss in AMD.

The [Formula: see text]-Wave of the Electroretinogram and Iron-Induced Oxidative Stress: A Model.

In photoreceptors of a dark adapted eye, the inward flux of sodium and calcium ions in the outer segment is balanced by the outward flux of potassium ions. But in the presence of light the creation of cyclic guanosine monophosphate in the outer segment decreases. Due to low concentration of cG (cyclic GMP) the channels in the outer segment open relatively less and thus the influx of calcium ion decreases, leading finally to hyperpolarization of the photoreceptors. We have analyzed theoretically the effect of oxidizing iron ions on the photoreceptors. In order to explain the effects of iron-induced oxidative stress, the different molecules and ions involved in phototransduction are quantified leading to a differential equation for calculating the electroretinogram a-wave voltage. The theoretical results are compared with published experimental data. In the presence of light, the iron ions could push outward the similarly charged calcium ions resulting in a small increase in the amount of inward calcium flux. Again, the presence of iron ions generates Reactive Oxygen Species, and ROS could attract the calcium ions which also increases the calcium flux. This will result in a reduction in the amplitude and slope of the a-wave voltage in the electroretinogram. These results are parametrized in terms of calcium ion concentrations. As the amplitude of the a-wave shows how much electrical signal is produced, its reduction indicates reduction in the visual signal. Thus, the increase in iron ions could explain the reduction in the electrical signal due to iron-induced oxidative stress.