Arteriolar involvement in the microvascular lesions of diabetic retinopathy: implications for pathogenesis

Diabetic retinopathy (DR) is the most widespread complication of diabetes mellitus and a major cause of blindness in the working population of developed countries. The clinicopathology of the diabetic retina has been extensively studied, although the relative contribution of the various biochemical and molecular sequelae of hyperglycemia remains ill defined. Many neural and microvascular abnormalities occur in the retina of short-term diabetic animals but it remains uncertain how closely these acute changes relate to chronic human disease. It is important to determine the relationship between alterations observed within the first weeks or months in short-term animal models, and human disease, where clinically manifest retinopathy occurs only after durations of diabetes measured in years. This review is focused on the retinal microvasculature, although it should be appreciated that pathological changes in this system often occur in parallel with abnormalities in the neural parenchyma that may be derivative or even causal. Nevertheless, it is useful to reevaluate the microvascular lesions that are manifest in the retina during diabetes in humans and long-term animal models, since in addition to providing useful clues to the pathogenic basis of DR as a disease entity, it is in the deterrence of such changes that the efficacy of any novel treatment regimes will be measured. In particular, an emphasis will be placed on the relatively unappreciated role of arteriolar dysfunction in the clinical manifestations and pathology of this disease.