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M Azuma, K Mizutani, C Fukiage, TR Shearer; Contribution of Ubiquitous Calpains to Cataractgenesis in Spontaneously Diabetic WBN/Kob Rat . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3589.
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Purpose: Calpains are a family of non-lysosomal cysteine proteases comprised of ubiquitous calpains (m-calpain and calpain 10) and tissue-specific calpains (Lp82). Possible synergistic relationships may exit between Lp82 and ubiquitous m-calpain in selenite-induced cataract in young rats. To determine involvement of calpains in human cataractogenesis, studies in aged animal models need to be performed since Lp82 is found only in young rodent lenses. Aged male WBN/Kob rats spontaneously develop cataract along with severe, persistent diabetes with hyperglycemia and nephropathy. Thus, the purpose of present experiments was to provide a biochemical mechanism for the involvement of ubiquitous calpains in cataractogenesis in WBN/Kob rats. Methods: Casein zymography, immunoblot analysis and calcium determinations were performed on lens samples from several ages of WBN/Kob and Wister rats. Results: Blood glucose levels increased and cortical cataract developed in male WBN/Kob rats within 1 year, indicating diabetic cataract. Cataract was accompanied by several presumptive biochemical indicators of calpain activation, including increased calcium, proteolysis of alpha-spectrin (a sensitive substrate for calpains), and decreased caseinolytic activity for calpains (suggesting calpain activation followed by autolytic degradation). Conclusions: Activation of ubiquitous calpains, but not lens-specific calpain Lp82, may contribute to biochemical mechanism of cataractogenesis in spontaneously diabetic WBN/Kob rats. Since Lp82 is not found in human lens or aged rodent lenses, the WBN/Kob model may be useful for elucidating the roles of m-calpain and calpain 10 in human cataractogenesis.
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