Effect of aldose reductase inhibition and insulin treatment on retinal capillary basement membrane thickening in BB rats.
This study compared the effect of glycemic control with insulin to that of the aldose reductase inhibitor ponalrestat on capillary basement membrane thickening in the retinas of diabetic BB rats. Diabetic animals with or without ponalrestat treatment were compared with diabetic rats subjected to vigorous insulin therapy or nondiabetic control rats with or without ponalrestat treatment after 6 mo of follow-up. Untreated diabetic animals showed the characteristic capillary basement membrane thickening in both the superficial and deep capillary beds of the retina. Vigorous blood glucose control with insulin therapy was accompanied by a complete prevention of capillary basement membrane thickening in both capillary beds, whereas aldose reductase inhibitor treatment achieved a complete prevention of basement membrane thickening in the deep capillary bed but not in the superficial capillary bed of the diabetic retina. These findings suggest that the mechanisms responsible for capillary basement membrane thickening in diabetes may be varied and modulated by topographical peculiarities in various capillary beds.
Chakrabarti
S
S
Department of Pathology, University of Manitoba, Winnipeg, Canada.
Sima
A A
AA
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000648:ultrastructure; D001786:Blood Glucose / Q000032:analysis; D002196:Capillaries / Q000187:drug effects / Q000648:ultrastructure; D002908:Chronic Disease; D003930:Diabetic Retinopathy / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D010793:Phthalazines / Q000627:therapeutic use*; D011724:Pyridazines / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D011913:Rats, Inbred BB; D012171:Retinal Vessels / Q000187:drug effects* / Q000648:ultrastructure; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010793:Phthalazines; D011724:Pyridazines; C042829:ponalrestat; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase