Increased ocular blood flow and ¹²⁵I-albumin permeation in galactose-fed rats: Inhibition by sorbinil

¹²⁵I-Albumin permeation and blood flow (assessed with 15 μm, ⁸⁵Sr-labelled microspheres) were determined in the retina, choroid, anterior uvea, and brain of male Sprague-Dawley rats fed diets containing 50% dextrin (control) or 50% galactose. Blood flow increased in the retina, choroid, and anterior uvea but not in the brain of rats fed galactose for 3 weeks and 3 months versus controls, and was normalized by sorbinil (an inhibitor of aldose reductase) in the 3-week group. After 8 months of galactose feeding, blood flow was reduced to normal levels in the retina and was slightly below normal in the choroid; blood flow remained elevated in the anterior uvea but was significantly lower than that observed at 3 weeks and at 3 months. In rats fed galactose for 8 months, sorbinil completely normalized blood flow in the choroid, and decreased, but did not normalize, blood flow in the anterior uvea. ¹²⁵I-Albumin permeation was increased in the retina, choroid, and anterior uvea of rats fed 50% galactose for 3 weeks, 3 months, and 8 months versus controls, but was unchanged in the brain. Sorbinil normalized ¹²⁵I-albumin permeation in all three ocular tissues in 8-month galactose-fed rats. Polyol levels were increased significantly in all three ocular tissues of 3-week galactose-fed rats; sorbinil markedly decreased, but did not normalize, polyol levels in all three tissues. These findings: (1) indicate that ocular blood flow is transiently increased, whereas albumin permeation increases are sustained in rats fed galactose-enriched diets for 8 months; (2) provide evidence that increased vascular ¹²⁵I-albumin permeation induced by galactose-feeding cannot be attributed entirely to increased blood flow; and (3) support the hypothesis that increased (vascular) metabolism of hexoses to polyols (induced by diabetes and by galactose ingestion) results in impaired vascular hemodynamics and loss of barrier functional integrity.