Effect of Aldose Reductase Inhibitor Fidarestat on Diabetic Ocular Complications in Spontaneously Diabetic Torii Rats

Abstract

Purpose: : To evaluate effects of an aldose reductase inhibitor, fidarestat, on development of diabetic retinopathy and cataract in spontaneously diabetic Torii (SDT) rats, an animal model of diabetic ocular complications.

Methods: : The rats were divided as follows: low-dose fidarestat group (8 mg/kg/day, n=14), high-dose fidarestat group (32 mg/kg/day, n=21), and untreated group (n=18). Diabetic retinopathy was evaluated by fluorescein angiomicroscopy and histopathology. Cataract was evaluated by biomicroscopy. Sorbitol levels in the retina and lens and vascular endothelial growth factor (VEGF) levels in ocular fluid were measured 40 weeks after the onset of diabetes.

Results: : Diabetic retinopathy did not develop in the low-dose (0/12 eyes, 0%) (p<0.001) and high-dose fidarestat groups (0/21 eyes, 0%) (p<0.00001) compared with the untreated group (12/17 eyes, 70.6%). Cataract developed less often in the low-dose (4/10 eyes, 40%) (p<0.01) and high-dose fidarestat groups (1/13 eyes, 7.7%) (p<0.00001) compared with the untreated group (12/12 eyes, 100%). Retinal and lens sorbitol levels were lower in the low-dose (2.7±1.1 and 30.0±3.3 nmol/mg protein, n=3, respectively) (p<0.01) and high-dose fidarestat groups (0.7±0.2 and 5.9±0.6 nmol/mg protein, n=4, respectively) (p<0.01) compared with the untreated group (23.2±4.7 nmol/mg protein, n=3). VEGF levels were lower in the low-dose (65.3±4.5 pg/ml, n=6) (p<0.05) and high-dose fidarestat groups (47.7±10 pg/ml, n=9) (p<0.01) compared with the untreated group (324.7±76.4 pg/ml, n=8).

Conclusions: : Fidarestat reduced the levels of sorbitol in the retina and lens and VEGF levels in the ocular fluid. Fidarestat prevented or delayed development of diabetic retinopathy and cataract in SDT rats.

Keywords: diabetic retinopathy