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A new approach against sugar cataract through aldose reductase inhibitors
S Banditelli1, E Boldrini, P G Vilardo
1Università di Pisa, Dipartimento di Fisiologia e Biochimica, Laboratorio di Biochimica, via S. Maria, 55, Pisa, 56100, Italy.
Abstract:
Aldose reductase inhibition is one of the therapeutic strategies that has been proposed to prevent or ameliorate long term diabetic complications including retinopathy and sugar cataract. Rats were fed with a galactose rich diet and the aldose reductase inhibitor Tolrestat was topically delivered by ocular instillation. The levels of lens aldose reductase activity, galactitol and the onset of cataract were evaluated during and after treatment with the inhibitor. Topical application of 1-3% Tolrestat (10 microl) four times daily resulted, after 9 days, in a significant decrease in the enzyme activity. Well after interrupting treatment with the drug, the enzyme activity remained impaired and galactose induced cataract was prevented. Our findings may represent the basis for therapeutic plans to prevent sugar cataract by long term cyclic treatments with aldose reductase inhibitors, with reduction in drug doses and side effects.
Insights
Aldose reductase inhibition can prevent sugar cataracts in rats. Topical Tolrestat treatment reduced enzyme activity, preventing cataract formation even after stopping the drug.
Area of Science:
- Biochemistry
- Ophthalmology
- Pharmacology
Background:
- Diabetic complications like retinopathy and cataracts are linked to aldose reductase activity.
- Aldose reductase inhibition is a potential therapeutic strategy for these conditions.
Purpose of the Study:
- To investigate the efficacy of topical aldose reductase inhibitor (Tolrestat) in preventing galactose-induced cataracts in rats.
- To evaluate the impact of Tolrestat on lens aldose reductase activity and galactitol levels.
Main Methods:
- Rats were fed a galactose-rich diet to induce cataracts.
- Tolrestat was administered via ocular instillation (1-3% solution, 10 microl, 4 times daily).
- Lens aldose reductase activity, galactitol levels, and cataract onset were monitored during and after treatment.
Main Results:
- Topical Tolrestat significantly decreased lens aldose reductase activity within 9 days.
- Cataract formation was prevented in rats treated with Tolrestat.
- The reduction in enzyme activity persisted even after the treatment was discontinued.
Conclusions:
- Topical aldose reductase inhibition is effective in preventing sugar cataracts.
- Cyclic, long-term treatment with aldose reductase inhibitors may offer a therapeutic approach for diabetic cataracts.
- This strategy could allow for reduced drug dosages and fewer side effects.