Abstract
Purpose:
Diabetic retinopathy is characterized by hypoxia in the retinal periphery and accompanying dilatation of the larger vessels in the central retina. Previous studies have shown that cyclooxygenase (COX) and nitric oxide (NO) modify the regulation of retinal vessel diameters during hypoxia in vitro and in vivo under normal conditions. The aim of the present study was to examine whether this could be reproduced in diabetic patients and thereby potentially point to new treatment strategies for vascular changes in diabetic retinopathy.
Methods:
Twenty diabetic patients aged 20-30 years without diabetic retinopathy were examined using the Dynamic Vessel Analyzer (DVA). The resting diameter and the diameter response secondary to isometric exercise and flicker stimulation of retinal vessels were studied before and during breathing of a hypoxic gas mixture. The examinations were performed before and during intravenous infusion with the NOS inhibitor L-NMMA and all examinations were repeated on a second day after administration of the COX-inhibitor diclofenac as eye drops.
Results:
The resting diameters of retinal vessels decreased significantly during L-NMMA infusion and increased significantly during hypoxia with and without L-NMMA infusion (p<0.0001 for all comparisons), but was not affected by diclofenac (p=0.27). Contraction of arterioles during isometric exercise decreased significantly during hypoxia and L-NMMA infusion separately and together (p=0.02), but was not significantly affected by diclofenac (p=0.08). The dilatations of arterioles during flicker stimulation was significantly reduced during hypoxia (p<0.0001), but was not affected by neither L-NMMA infusion nor diclofenac (p>0.05).
Conclusions:
NO products are involved in the regulation of retinal vessel diameter in diabetic patients. These mechanisms of action may be used as targets for normalizing pathologic diameter changes of retinal vessels in diabetic retinopathy.