Rod photoreceptor activation and deactivation in early-stage diabetic eye disease

Abstract

Purpose: To infer rod phototransduction activation and deactivation characteristics in diabetics who have mild or no clinically-apparent retinopathy.

Methods: Fifteen non-diabetic controls, 15 diabetics with no clinically-apparent diabetic retinopathy (NDR), and 15 diabetics with mild non-proliferative diabetic retinopathy (MDR) participated. Dark-adapted flash electroretinograms (3.2 to 4.4 log scot td-s) were recorded to assess rod activation. The a-waves were fit with a Gaussian model to derive R_mp3 (maximum photoreceptor response amplitude) and S (phototransduction sensitivity). Rod deactivation was assessed with a paired flash paradigm, in which a-waves were measured for two flashes separated by inter-stimulus intervals (ISIs) of 0.125 to 16 s. The ISI needed for the a-wave amplitude of the second flash to recover to 50% of the first flash (t₅₀) was determined. The effect of stimulus retinal illuminance on activation and deactivation was evaluated in a subset of control subjects.

Results: Analysis of variance indicated that both diabetic groups had significant log S reductions compared to controls (p < 0.001). Mean S was reduced by approximately 49% and 78% for the NDR and MDR groups, respectively. In contrast, log R_mp3 and log t₅₀ did not differ significantly among the groups (both p > 0.08). Reducing stimulus retinal illuminance significantly reduced S, but did not significantly affect R_max or t₅₀.

Conclusions: Only phototransduction sensitivity was abnormal in this sample of diabetic subjects. The normal deactivation kinetics suggests that circulating rod current is normal. These findings begin to constrain possible explanations for abnormal rod function in early diabetic retinal disease.

Keywords: Diabetic retinopathy; Electroretinogram; Photoreceptors; Rod function.

Figure 1:

Mean single flash ERG waveforms recorded from control subjects (solid black), NDR subjects (solid green), and MDR subjects (solid red) at four retinal illuminances (3.2 log Td-s to 4.4 log Td-s). The dashed lines represent the delayed Gaussian model (Eq. 1) fit to the traces of the corresponding color.

Figure 2:

Log R_mp3 (left) and log S (right) are shown for each control subject (black), NDR subject (green circles), and MDR subject (red). The horizontal bars mark the group means.

Figure 3:

Mean single flash a-waves for the control subjects (left), NDR subjects (middle), and MDR subjects (right) are shown. Within each panel, each trace represents the response to a single flash (black) or to the second response of a flash pair, with the ISI indicated in the color coded key.

Figure 4:

The mean (±SEM) normalized a-wave amplitude (second flash a-wave / first flash a-wave) is plotted as a function of ISI for the control (black), NDR (green), and MDR (red) subjects. The solid lines are the fits of Eq. 2 to the data. The right panel shows the log t₅₀ value for the controls (black), NDR subjects (green), MDR subjects (red). The horizontal bars mark the group means.

Figure 5:

The effect of reducing the stimulus retinal illuminance is shown for log R_mp3 (top), log S (middle), and log t₅₀ (bottom). Each symbol represents a different control subject (horizontal bars mark the group means) for measurements obtained with the original flash retinal illuminances (3.2 to 4.4 log Td-s) and for flashes of half the original retinal illuminances (2.9 to 4.1 log scot Td-s).