We examined the effects of
GP-1447 (3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]-5-methylphenyl
acetic acid) on existing
cataracts and
sorbitol content in the lens in rats with
streptozotocin-induced diabetes.
GP-1447 is an inhibitor of
aldose reductase, which is the first
enzyme in the
polyol pathway.
Cataracts in the central region of the lens were observed in 7 of 14 eyes (50%) by the fifth week after induction of diabetes, and development of mature
cataracts was observed in most
lenses by the ninth week. In diabetic rats that received
GP-1447 treatment beginning in the fifth week after induction of diabetes, progression of
cataracts was observed for 1 week after initiation of treatment. Thereafter, the severity of
cataracts did not change substantially.
Sorbitol levels in the lens peaked during the first week of diabetes, and this increase was maintained during the 9-week observation period. Elevated
sorbitol levels in the
lenses of diabetic rats gradually declined after
GP-1447 treatment was started on the fifth week after induction of diabetes.
Cataracts and
sorbitol elevation were not observed in the
lenses of controls or diabetic rats treated with
GP-1447 immediately after induction of diabetes. These results suggest that the
polyol pathway plays an important role in both the appearance and progression of
cataracts in diabetic rats. Inhibition of
aldose reductase could significantly prevent progression of existing
cataracts.