Nicotine Exposure Exacerbates Development of Cataracts in a Type 1 Diabetic Rat Model

Abstract

Purpose: : It is well known that the incidence of cataract is higher in diabetics as compared to non-diabetics. The rates of maturation of cataracts are also faster in diabetics. However, the presence of any synergetic effects between smoking and diabetes on the rate of cataract maturation has not been established yet. To examine the relation between cigarette smoking and acceleration of cataract formation in diabetics, we evaluated the influence of chronic nicotine exposure on the development of cataracts in a type 1 diabetic rat model.

Methods: : Forty-five male Sprague-Dawley rats were divided into 4 groups: 1) diabetic with nicotine treatment, 2) diabetic without nicotine treatment, 3) controls with nicotine treatment, and 4) controls without nicotine treatment. Diabetes was induced with IP streptozotocin at 60 mg/kg in sodium citrate (pH 4.5), and body weights and nonfasting blood glucose were measured weekly. Nicotine hydrogen tartrate salt was administered subcutaneously to groups 1 and 3 daily. An initial up-titrating dose was initiated starting from 0.3 mg/kg to a final dose of 2.1 mg/kg, which was continued until termination of the experiment. Cataracts were graded with a Nikon camera at week 9 (experiments 1& 2) and at weeks 10 and 11 (experiment 2) by a masked grader using the Oxford classification system. Cytokines were measured on an aliquot of plasma obtained at termination of the experiment.

Results: : In experiment 1, cataract scores after 9 weeks of nicotine treatment were increased in the diabetes plus nicotine treatment group as compared to the diabetes only group (p =0.038). In experiment 2, cataract scores were similarly increased in the diabetes plus nicotine treatment group as compared to the untreated diabetic group at 9 weeks (p =0.019). The cataract score continued to be greater in the diabetes plus nicotine treatment group versus the untreated diabetic group at 10 weeks (p = 0.0015) and 11 weeks (p = 0.0004). Nicotine treatment alone had no effect on cataract development in animals enrolled in this study. Serum MCP-1 and RANTES were decreased in diabetic with nicotine treatment as compared to diabetic without treatment (p<0.001).

Conclusions: : There is an increase in the severity of cataract scores in the nicotine-treated diabetic vs untreated diabetic rats. The observed synergism of nicotine in the presence of hyperglycemia in promoting cataract progression may be related to altered cytokine regulation and oxidative stress. Our observations have implications for diabetics who smoke or utilize nicotine patches.

Keywords: cataract • diabetes • ocular irritancy/toxicity testing