Abstract
Purpose :
To understand the roles of glucose and pH in changes of the ERG during diabetes.
Methods :
Vitreal ERG recordings were performed in control and diabetic Long-Evans rats 3 to 60 weeks after IP vehicle or streptozotocin. Animals were dark-adapted and light flashes of various intensities were long enough (2.5 s) to produce c-waves. Blood glucose was manipulated by intravenous glucose or insulin. H+-selective microelectrodes were used to measure retinal pH. To mimic the diabetes-induced acidosis in controls, the retinal pH was decreased by NH4. A decrease of retinal pH was also achieved by injection of the carbonic anhydrase blocker dorzolamide.
Results :
During development of diabetes the b-wave amplitude progressively decreased (0.53±0.06 mV after a year vs 1.12±0.03 mV in controls). In contrast, the c-wave was strongly affected from the beginning of diabetes. In controls, the c-wave was cornea-positive at scotopic illuminations, but cornea-negative in the lower photopic range (-0.10±0.03 mV). In diabetics, the whole amplitude-intensity curve was shifted toward negativity, and the c-wave photopic amplitude was -0.50±0.04 mV after 3-9 weeks of diabetes. Experimentally induced acidification of control retinae had no significant effects on the b-wave and shifted the c-wave toward positivity. A similar positive shift of the c-wave was observed when diabetic retinae were acidified. But controls and diabetics responded differently to glucose manipulations. Elevation of blood glucose in controls did not affect the ERG. In diabetics, an increase of blood glucose immediately shifted the c-wave toward more negativity (the photopic c-wave was -0.90±0.26 mV), and a decrease of blood glucose with insulin had the opposite effect (c-wave was -0.30±0.11 mV).
Conclusions :
The steady decrease of the b-wave during development of diabetes probably reflects general degradation of the retinal neurons. Changes in the c-wave are more complex, which is understandable because several different cellular elements contribute to its generation. The most striking feature of the diabetic ERG – significant negativity of c-wave – is strongly correlated with glucose, but not with pH. A number of reasons can be offered to explain why the K+-dependent cornea-positive response of the retinal pigment epithelium decreases or the K+-dependent cornea-negative response of the glial Muller cells increases with elevation of glucose in diabetics, but not in controls.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.