Differential diameter responses in macular and peripheral retinal arterioles may contribute to the regional distribution of diabetic retinopathy lesions

Background Diabetic retinopathy is assumed to be due to impaired retinal autoregulation, involving both pressure autoregulation and metabolic autoregulation. The disease displays regional differences, with signs of hyperperfusion in the macular area and capillary occlusion with retinal ischemia in the peripheral retinal areas. It can be hypothesized that these regional differences in the occurrence of retinopathy lesions may reflect differences in the capacity of retinal arterioles to autoregulate the diameter of retinal arterioles. Methods Seventeen normal persons and two matched groups of patients with respectively diabetic maculopathy and proliferative diabetic retinopathy were examined. The diameter change of a macular and a peripheral retinal arteriole during an increase in the arterial blood pressure induced by isometric exercise, during an increase in retinal metabolism induced by flicker stimulation, and during both stimulus paradigms simultaneously were studied using the dynamic vessel analyzer (DVA). Results During isometric exercise, the diameter response was reduced in both macular and peripheral retinal arterioles in the two groups of patients with diabetes mellitus. During flicker stimulation, the diameter response was significantly reduced in patients with proliferative diabetic retinopathy, but there was no significant difference between the responses of macular and peripheral arterioles. During simultaneous isometric exercise and flicker stimulation, there was no difference between the diameter response of macular arterioles in the three groups, whereas the diameter response of macular arterioles was significantly lower in normal persons and significantly higher in persons with proliferative diabetic retinopathy as compared to peripheral arterioles. Conclusions Regional differences in the disturbances of the diameter response to increased blood pressure may contribute to the regional differences in the distribution of diabetic retinopathy lesions. In the central retinal areas, the diameter response to increased blood pressure and retinal metabolism interacted in a way that may potentially protect this area from ischaemia, whereas this protective mechanism was absent in the peripheral retinal arterioles. An elucidation of the mechanisms underlying diameter regulation to increased blood pressure and retinal metabolism, and the interaction between these two mechanisms, may help in understanding the pathophysiology of diabetic retinopathy.