Hypoxia and Dark Adaptation in Diabetic Retinopathy: Interactions, Consequences, and Therapy

In diabetes, retinal blood flow is compromised, and retinal hypoxia is likely to be further intensified during periods of darkness. During dark adaptation, rod photoreceptors in the outer retina are maximally depolarized and continuously release large amounts of the neurotransmitter glutamate—an energetically demanding process that requires the highest oxygen consumption per unit volume of any tissue of the body. In complete darkness, even more oxygen is consumed by the outer retina, producing a steep fall in the retinal oxygen tension curve which reaches a nadir at the depth of the mitochondrial-rich rod inner segments. In contrast to the normal retina, the diabetic retina cannot meet the added metabolic load imposed by the dark-adapted rod photoreceptors; this exacerbates retinal hypoxia and stimulates the overproduction of vascular endothelial growth factor (VEGF). The use of nocturnal illumination to prevent dark adaptation, specifically reducing the rod photoreceptor dark current, should ameliorate diabetic retinopathy.