Experimental diabetes mellitus impairs the function of the retinal pigmented epithelium

The retinal pigmented epithelium (RPE), which influences the composition of the retinal extracellular fluid, is significantly affected in diabetes. Changes in RPE morphology, permeability, and electrophysiology in experimentally diabetic animals have been described. To facilitate the study of diabetes-related changes in RPE metabolism, we applied the techniques of quantitative histochemistry to pure samples of RPE and individual retinal layers from eyes of normal and alloxan-diabetic rabbits. Glucose within the RPE approximated serum levels in both normal and diabetic animals. Other changes in diabetics included increased sorbitol, decreased myo-inositol, elevated total Na, and loss of measurable Na+-K+-ATPase activity within the RPE. The altered ion metabolism was associated with a progressive decrease in the amplitude of the RPE-generated c-wave of the electroretinogram. The deterioration of the c-wave was arrested by treatment of the diabetic animals with either myo-inositol supplementation or with sorbinil, an inhibitor of aldose reduction. Diabetic alterations in the RPE might impair the ability of the tissue to maintain normal transport functions. The subsequently altered composition of the extracellular environment of the retina may play an important role in the pathogenesis of diabetic retinopathy.