Cataract Formation Is Prevented by Administration of Verapamil to Diabetic Rats*

Abstract

The purpose of the present study was to examine the effects on cataractogenesis of daily sc administration of the Ca2+ antagonist drug verapamil to diabetic rats. Streptozotocin-induced diabetic rats were given verapamil half-way through the 8-week experimental period or during the full 8 weeks of diabetes. Verapamil administration had no effect on the high blood glucose values, low circulating insulin levels, or elevated triglyceride and cholesterol concentrations in the diabetic rats. Untreated diabetic rats had a 90% incidence of cataracts. Four weeks of verapamil administration reduced this incidence to 41%, and a full 8 weeks of drug treatment further lowered the incidence to 20%. Diltiazem, another Ca2+ antagonist, lowered the incidence of cataracts in the diabetic rats to a similar extent. Verapamil administration to the diabetic animals also partially protected against the presence of retinal microangiopathy in the diabetic animals. Lenticular hydration and lipid accumulation were only indirectly related to cataractogenesis in the diabetic rats and its protection by verapamil treatment. Lenticular electrolyte imbalance, particularly Ca2+, in the diabetic animals was closely correlated with cataract formation, and verapamil significantly reduced the alterations in these ion concentrations. The present results demonstrate the efficacy of verapamil as a protective agent against cataractogenesis and some retinal damage in diabetic animals. Most importantly, this occurs in the absence of any change in the glycemic status of the diabetic animals. The findings strongly support a role for lenticular Ca2+ imbalance in cataract development in diabetes and provide initial evidence to suggest its clinical use in the diabetic population at risk for blindness.

Effect of Nifedipine on Severe Experimental Cataract in Diabetic Rats

“…The concentration of verapamil we adopted has been shown to reduce the incidence of diabetic cataracts measured after 8 weeks of hyperglycemia from 90% to 20% in a previous study (20). However, in the present study, verapamil failed to prevent significantly the onset and progression of diabetic cataracts.…”

“…Previous studies have demonstrated that verapamil exerts an inhibitory effect on diabetic cataracts in rats (20,22,23). The concentration of verapamil we adopted has been shown to reduce the incidence of diabetic cataracts measured after 8 weeks of hyperglycemia from 90% to 20% in a previous study (20).…”

“…To examine the effects of nifedipine and verapamil on the cataract formation in diabetic rats, 9 diabetic rats were fed on chow containing 0.1% w / w nifedipine (Bayer Yakuhin, Ltd., Osaka) and 9 diabetic rats were injected with verapamil (Sigma) twice a day at 9:00 am (3 mg / kg, s.c.) and 5:00 pm (6 mg / kg, s.c) (20). To determine the concentration of nifedipine, we tested the effects of chows containing three different concentrations of nifedipine (0.03%, 0.1%, and 0.3% w / w) in a pilot study.…”

“…Since both systemic and topical administration of verapamil, an L-type Ca 2+ -channel blocker, have been reported to prevent cataract formation in diabetic rats (20,22,23), Ca 2+ influx into lens cells via L-type Ca 2+ channels has been suggested to be involved in the mechanism of this process. Although the detailed mechanism for how elevated Ca 2+ in the lens induces cataracts is not understood, activation of Ca 2+ -dependent proteins, such as calpain (25); impairment of cell communication among lens fibers (26); changes in lens permeability (27); loss and / or cleavage of some proteins (28,29); and formation of high moleculer weight proteins (30) have been suggested.…”

Lenticular Calcium, Magnesium, and Iron Levels in Diabetic Rats and Verapamil Effect

“…However, it has also been stated that a breakdown in phosphoinositide metabolism destroys the structure of the lens, which in turn leads to cataract formation [4]. Recent research efforts have focused on lens electrolyte imbalances in diabetic cataract [5]. We have analyzed the ion alterations in diabetic rats and the effects of the Ca channel blocker verapamil.…”