Systemic Reduction of Glut1 Normalizes Retinal Dysfunction, Inflammation, and Oxidative Stress in the Retina of Spontaneous Type 2 Diabetic Mice.

Defects in the light-evoked responses of the retina occur early in the sequalae of diabetic retinopathy (DR). These defects, identified through the electroretinogram (ERG), represent dysfunction of retinal neurons and the retinal pigment epithelium and are commonly identifiable at the timing of, or almost immediately following, diabetes diagnosis. Recently, systemic reduction of the facilitated glucose transporter type 1, Glut1, in type 1 diabetic mice was shown to reduce retinal sorbitol accumulation, mitigate ERG defects, and prevent retinal oxidative stress and inflammation.

Reduction of Glut1 in the Neural Retina But Not the RPE Alleviates Polyol Accumulation and Normalizes Early Characteristics of Diabetic Retinopathy.

Hyperglycemia is a key determinant for development of diabetic retinopathy (DR). Inadequate glycemic control exacerbates retinopathy, while normalization of glucose levels delays its progression. In hyperglycemia, hexokinase is saturated and excess glucose is metabolized to sorbitol by aldose reductase via the polyol pathway.

Endogenous insulin signaling in the RPE contributes to the maintenance of rod photoreceptor function in diabetes.

In diabetes, there are two major physiological aberrations: (i) Loss of insulin signaling due to absence of insulin (type 1 diabetes) or insulin resistance (type 2 diabetes) and (ii) increased blood glucose levels. The retina has a high proclivity to damage following diabetes, and much of the pathology seen in diabetic retinopathy has been ascribed to hyperglycemia and downstream cascades activated by increased blood glucose. However, less attention has been focused on the direct role of insulin on retinal physiology, likely due to the fact that uptake of glucose in retinal cells is not insulin-dependent.