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N. H. Ansari, M. Zhang, V. U. L. Mokkapati, T. Xiao, G. A. Campbell; Potential of Metal Chelation Therapy in the Delay of Diabetic Cataract. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3186.
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The transition metal ions have been implicated in the generation of reactive oxygen species (ROS) causing increased oxidative stress leading to pathological conditions such as diabetic cataract. Elevated levels of chelatable pool of redox-active metal ions have indeed been shown to be present at increased concentrations in aged and cataractous lenses. However, metal chelation attempts to prevent cataractogenesis have been limited due to the permeability barrier of the cell membrane to the metal chelators. To investigate the efficacy of chelation therapy against diabetic cataract, we have therefore topically used the metal chelator, EDTA, in conjunction with a permeability enhancer, methylsulfonylmethane (MSM)
Part A of this study was to evaluate the entry of EDTA into the lens when topically applied to the rat eye in the presence of MSM. Radiolabeled EDTA and Sprague Dawley rats were used for these studies. Part B of the study was to topically treat the eyes of the diabetic rats with various concentrations of EDTA + MSM and evaluate the efficacy and mechanism of EDTA to prevent/ameliorate diabetic cataractogenesis.
Part A of our studies demonstrated that EDTA in the presence of MSM enters into the aqueous and the lens. Part B of our studies demonstrated a significant amelioration of cataractogenesis by topical application of EDTA+MSM onto the diabetic rat eye. Oxidative markers, which were increased in the diabetic rat lens, significantly normalized in the lenses of the diabetic rat which were treated with EDTA + MSM.
EDTA in the presence of MSM can enter into the lens when topically applied onto the eye. Furthermore, it appears that "excess metals" in diabetes trigger the oxidative stress and contribute to cataractogenesis. Chelation therapy using EDTA+MSM can be a promising clinical therapy for protecting against diabetic cataracts.
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