Diabetes-Induced Changes of the Rat ERG in Relation to Hyperglycemia and Acidosis

To understand the mechanism of changes in the c-wave of the electroretinogram (ERG) in diabetic rats, and to explore how glucose manipulations affect the c-wave.

Vitreal ERGs were recorded in control and diabetic Long-Evans rats, 3-60 weeks after IP vehicle or streptozotocin. A few experiments were performed on Brown Norway rats. Voltage responses to current pulses were used to measure the transepithelial resistance of the retinal pigment epithelium (RPE).

During development of diabetes the b-wave amplitude progressively decreased to about half of the initial amplitude after a year. In contrast, the c-wave was strongly affected from the very beginning (3 weeks) of diabetes. In control rats, the c-wave was cornea-positive at lower illuminations but was cornea-negative at higher (photopic) illumination. In diabetics, the whole amplitude-intensity curve was shifted toward negativity. The magnitude of this shift was markedly affected by acute glucose manipulations in diabetics but not in controls. Increased blood glucose made the c-wave more negative, and decreased blood glucose with insulin had the opposite effect. Experimentally induced acidification of the retina had a small effect that was different from diabetes, shifting the c-wave toward positivity, slightly in controls and more noticeably in diabetics. One reason for the significant negativity of the diabetic ERG was a decrease of the cornea-positive response of the RPE due to a decrease of the transepithelial resistance.

The ERG c-wave is more negative in diabetics than in control animals, and is far more sensitive to changes in blood glucose. The increased negativity is largely if not entirely due to changes in the transepithelial resistance of the RPE, an electrical analog of the breakdown of the blood-retinal barrier observed in other studies. The sensitivity of the c-wave to glucose in diabetics may also be due to changes in transepithelial resistance.