Development of diabetes-induced acidosis in the rat retina

- We hypothesized that diabetic retinae would be acidic due to increased glycolysis.
- We measured [H+]o in retinae of control and diabetic rats with H+ microelectrodes.
- In controls, [H+]o in the outer nuclear layer is about 30 nM higher than in blood.
- Retinae were more acidic from 1 to 3 months of diabetes, but not before or after.
- [H+]o was more variable in diabetic retinae, both within and between animals.

We hypothesized that the retina of diabetic animals would be unusually acidic due to increased glycolytic metabolism. Acidosis in tumors and isolated retina has been shown to lead to increased VEGF. To test the hypothesis we have measured the transretinal distribution of extracellular H+ concentration (H+-profiles) in retinae of control and diabetic dark-adapted intact Long-Evans rats with ion-selective electrodes. Diabetes was induced by intraperitoneal injection of streptozotocin. Intact rat retinae are normally more acidic than blood with a peak of [H+]o in the outer nuclear layer (ONL) that averages 30 nM higher than H+ in the choroid. Profiles in diabetic animals were similar in shape, but diabetic retinae began to be considerably more acidic after 5 weeks of diabetes. In retinae of 1-3 month diabetics the difference between the ONL and choroid was almost twice as great as in controls. At later times, up to 6 months, some diabetics still demonstrated abnormally high levels of [H+]o, but others were even less acidic than controls, so that the average level of acidosis was not different. Greater variability in H+-profiles (both between animals and between profiles recorded in one animal) distinguished the diabetic retinae from controls. Within animals, this variability was not random, but exhibited regions of higher and lower H+. We conclude that retinal acidosis begins to develop at an early stage of diabetes (1-3 months) in rats. However, it does not progress, and the acidity of diabetic rat retina was diminished at later stages (3-6 months). Also the diabetes-induced acidosis has a strongly expressed local character. As result, the diabetic retinas show much wider variability in [H+] distribution than controls. pH influences metabolic and neural processes, and these results suggest that local acidosis could play a role in the pathogenesis of diabetic retinopathy.