Aldose reductase and retinal capillary basement membrane thickening
W G Robison1, M Nagata, J H Kinoshita
1National Eye Institute, NIH, Bethesda, MD 20892.
Experimental Eye Research
|March 1, 1988
Summary
High galactose intake thickened retinal capillary basement membranes in rats, mimicking diabetic microangiopathy. An aldose reductase inhibitor prevented these changes, demonstrating its protective effect against galactose-induced vascular damage.
Area of Science:
- Biomedical Science
- Ophthalmology
- Diabetic Complications
Background:
- Diabetic microangiopathy is a serious complication of diabetes.
- Galactosemia can induce vascular changes similar to diabetic complications.
- Aldose reductase plays a role in polyol pathway metabolism and diabetic complications.
Purpose of the Study:
- To investigate the long-term effects of a high galactose diet on retinal capillaries.
- To evaluate the efficacy of an aldose reductase inhibitor in preventing galactose-induced vascular changes.
- To assess ultrastructural alterations in retinal capillaries under galactose-rich conditions.
Main Methods:
- Weanling male Sprague-Dawley rats were fed a 50% galactose diet for 88 weeks.
- Some rats received an aldose reductase inhibitor (tolrestat) concurrently.
- Retinal capillaries were analyzed using quantitative computer planimetry on electron micrographs.
Main Results:
- Galactose-fed rats exhibited significantly thickened retinal capillary basement membranes (263 +/- 50 nm).
- Rats treated with tolrestat showed reduced basement membrane thickness (153 +/- 10 nm) compared to untreated galactose-fed rats.
- Control rats had the thinnest basement membranes (114 +/- 16 nm).
- Ultrastructural changes, including multi-lamination and vacuoles, were observed in galactose-fed rats, resembling diabetic microangiopathy.
Conclusions:
- Long-term galactose feeding induces significant retinal capillary basement membrane thickening and ultrastructural damage.
- Aldose reductase inhibition effectively prevents these galactose-induced microvascular changes.
- These findings support the role of aldose reductase in the pathogenesis of diabetic microangiopathy.
