Abstract. The purpose of this study was to establish a novel imaging system for evaluation of cataract in small animals. Diabetic cataract was induced in male Wistar rats by a combination of a bolus injection of streptozotocin (65 mg/kg, i.v.) and 5% D-glucose given as drinking water. To assess cataract development, we designed a digital camera system equipped with a nonreflecting illuminator for capturing clear high-resolution full lens images in the horizontal plane. Cataract was evaluated from the resulting images using both an observer-based scoring system and quantitative digital image-analysis techniques. The onset of cataract was detected in the peripheral section of the lens in 57% of cases 2 weeks after induction of hyperglycemia. Central opacities were visible following 3 weeks in hyperglycemic conditions. The cataract increased in severity with time, so that by week 9 in hyperglycemic conditions, mature cataracts were developed in over 90% of lenses. Treatment of diabetic rats with GP-1447, an aldose reductase inhibitor, completely prevented the formation of diabetic cataracts. These results indicate that the digital imaging system established in the present study permits an assessment of all stages of cataract development and it is helpful for accurately evaluating the effects of therapeutic drugs on cataracts.

We examined the effect of nicorandil on retinal blood vessels in rats in vivo. Male Wistar rats (8 to 10 weeks old) were anaesthetised with thiobutabarbital (120 mg/kg, intraperitoneal). Fundus images were captured with a digital camera that was equipped with a special objective lens. Diameters of retinal blood vessels were measured with a personal computer. Nicorandil (1-300 microg kg(-1) min(-1), intravenous [i.v.]) increased diameters of retinal blood vessels and decreased systemic blood pressure in a dose-dependent manner. Both responses to nicorandil were attenuated by glibenclamide (20 mg/kg, i.v.), an adenosine triphosphate (ATP)-dependent K(+) (K(ATP)) channel blocker. On the other hand, indomethacin (5 mg/kg, i.v.), a cyclooxygenase inhibitor, attenuated the vasodilation of retinal blood vessels, but not depressor response, to nicorandil and sodium nitroprusside. Pinacidil (1-300 microg kg(-1) min(-1), i.v.), a K(ATP) channel opener, also dilated retinal blood vessels and decreased systemic blood pressure. The responses to pinacidil were prevented by glibenclamide, but not by indomethacin. The vasodilation of retinal arteriole, but not depressor response, to sodium nitroprusside (1-30 microg kg(-1) min(-1), i.v.), a nitric oxide donor, was attenuated by indomethacin. These results suggest that nicorandil dilates retinal blood vessels through opening of K(ATP) channels and production of prostaglandins that are probably generated by nitric oxide.

These results suggest that fasudil has beneficial effects on retinal vascular complications associated with chronic hypertension.

Abstract. We examined the effects of Ca 2+-channel blockers on sugar cataract formation in streptozotocin (65 mg / kg, i.v.)-induced diabetic rats that were given 5% D-glucose as drinking water. The diabetic rats were treated with an L-type Ca 2+-channel blocker, nifedipine or verapamil, for 9 weeks from the 3rd day of streptozotocin injection. Using the full lens images of the horizontal plane captured with the new digital camera system that we developed recently, the cataract formation was quantitatively assessed in parallel with the conventional scaling method. In the animal model of diabetes mellitus, the cataracts at the peripheral region of the lens were detected 2 weeks after induction of hyperglycemia and progressed depending on the length of the diabetic period. The majority of them developed mature cataracts after 9 weeks of hyperglycemia. Nifedipine slowed the progression rate of diabetic cataracts without affecting the period of time required for the onset of this disease, whereas verapamil had no significant inhibitory effect on the diabetic cataract. These findings suggest that nifedipine may be considered as a candidate drug to suppress the progression of diabetic cataracts.

The present study was undertaken to assess whether A-3922, a dihydrobenzofuran derivative that possesses antioxidative effects, had any preventive effect on the onset and/or progression of diabetic cataract. Male Wistar rats were received a bolus intravenous injection of streptozotocin (65 mg/kg) and were given 5% glucose in drinking water for 10 weeks. The diabetic rats were divided into two groups and treated with 30 mg/kg/d A-3922 or vehicle during the experimental period. The opacities of eye lenses were observed by using both our original device and a slit lamp microscope. The lens opacities were initially detected as early as the 2nd week and the cataracts were developed in similar fashion in both A-3922-treated and untreated diabetic rats until 7th week, suggesting that A-3922 did not show any appreciable effect on the onset of diabetic cataract. In the later period (8th week or later), however, progression of cataract was retarded and significant reductions in both the total cataract score and the degree of opacity were apparently observed on 10th week of A-3922-treated diabetic rats. These results suggest that A-3922 can delay the progression but not the onset of diabetic cataract, and it has a possibility to be a candidate for drugs of cataract associated with diabetes.