The authors investigate the effect of
aldose reductase inhibitor
FR74366 on diabetic
cataract.
Streptozocin (STZ)-induced diabetic rats were treated with
eye drops of
FR74366 (0.03%, 0.1%, and 0.3%) for 16 weeks.
Lenses were examined using a
slit lamp, and the score of
lens opacity was determined on a scale of from 0 (normal lens) to 4 (matured nuclear
cataract). Diabetic placebo control rats developed
lens opacity linearly, beginning at 3 weeks and reaching a maximum at 8 weeks after STZ injection. Instillation of
FR74366 to diabetic rats delayed the
cataract formation and inhibited lens
sorbitol accumulation in a dose-dependent manner. At 16 weeks after STZ injection, the score of
lens opacity was more than 3 (diffuse central opacities) in diabetic placebo control rats, whereas it was less than 2 (peripheral vesicles and cortical opacities) and the
lenses remained clear in animals treated with 0.3% of
FR74366. Measurement of tissue
drug concentrations indicated that
FR74366 penetrated into the lens, where its levels were increased in a dose- and time-dependent manner. These three parameters (score of
lens opacity and
sorbitol and
FR74366 levels) were well correlated with each other. Instillation of
FR74366 also reduced the
sorbitol levels in the retina. However, the
sorbitol levels in the sciatic nerve and renal cortex were not changed by instillation of
FR74366. Instillation or
oral administration of
FR74366 has not shown serious side effects in animal toxicity studies. These results suggested that instillation of
FR74366 may be a useful therapeutic agent against diabetic
cataract and retinopathy.