Polyol accumulation in cultured human lens epithelial cells
L R Lin1, V N Reddy, F J Giblin
1Eye Research Institute, Oakland University, Rochester, MI 48309-4401.
Experimental Eye Research
|January 1, 1991
Summary
Human lens epithelial cells exposed to D-galactose accumulated galactitol, forming vacuoles and losing myoinositol. Aldose reductase inhibitors prevented these changes, suggesting a role in diabetic cataract formation.
Area of Science:
- Ophthalmology
- Cell Biology
- Biochemistry
Background:
- Diabetic cataracts are a significant complication of diabetes.
- The polyol pathway is implicated in diabetic complications.
- Human lens epithelial (HLE) cells are a relevant model for studying cataractogenesis.
Purpose of the Study:
- To investigate the role of the polyol pathway in HLE cell changes.
- To examine the effects of D-galactose exposure on HLE cells.
- To evaluate the efficacy of aldose reductase inhibitors in preventing D-galactose-induced changes.
Main Methods:
- Culturing HLE cells in media with D-galactose or L-galactose.
- Utilizing transmission electron microscopy to observe cellular changes.
- Assessing the effects of aldose reductase inhibitors (sorbinil and AL 1576).
Main Results:
- D-galactose induced significant galactitol accumulation, vacuole formation, and myoinositol depletion in HLE cells.
- L-galactose, not a substrate for aldose reductase, did not cause these changes.
- Aldose reductase inhibitors, particularly AL 1576, prevented D-galactose-induced cellular alterations.
Conclusions:
- Vacuole formation in HLE cells is attributed to the osmotic effect of galactitol produced by aldose reductase.
- The polyol pathway is a key factor in the development of diabetic cataracts.
- AL 1576 demonstrates superior potency compared to sorbinil in inhibiting human lens aldose reductase.
