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MG Henein, KR Hegde, SD Varma; Pathophysiological Studies in Diabetic Mice Lens; A Low Aldose Reductase Model . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3590.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To study the development of lens hydration and cataract formation in mice with experimental diabetes and to examine its attenuation by pyruvate. Methods: Mice made diabetic with Streptozotocin were divided into two groups labeled as controls and experimentals. The controls received no treatment. Experimental group were given 1% pyruvate in food. The progress of cataract was monitored by regular slit-lamp examination, Scheimpflug photography and standard ophthalmoscopic techniques. Subsequently, mice were sacrificed, eyes enucleated and lenses isolated for histological and biochemical studies. Results: Blood glucose of all diabetic mice ranged between 350-400 mg/dl. The percentage of animals having cataracts after 4 weeks of diabetes was 29% in the control group and 15% in the pyruvate-treated group. At 8-9 weeks, 43% of diabetic animals in the control group and 25% in the treated group had cataracts. After 14-15 weeks, 82% of animals in the control group had dense cataracts. In the treated group the incidence was only 57%. Additionally, the cataracts in the latter group were minor, not interfering with retinal examination. Glucose level in the lens was 17±5.2nmoles/lens in the normal, 136±2.5nmoles/lens in the control diabetic, and 96±37nmoles/lens in the treated diabetic mice. The fructose levels were 4.4±0.6nmoles/lens in the normal, 9.2±1.8nmoles/lens in the control diabetic, and 8.6±0.43nmoles/lens in the pyruvate-treated group. Sorbitol was in trace amounts in the normal and the pyruvate-treated group, while it was elevated to 1.3±0.025nmoles/lens in the untreated diabetic control. Histologically, delayed cell maturation and persistence of nucleus in diabetic mice was similar to other forms of cataracts. While the level of sorbitol is insignificantly elevated in the diabetic lens, its synthesis was prevented by pyruvate. The lens hydration associated with diabetes was also prevented. Conclusion: Contrary to expectation, cataract formation was well discernible in these diabetic mice despite low lens aldose reductase activity. A dense cataract can be observed by about 4 months. Cataractogenic features were observed at the levels of cellular maturation and regional architecture. The gross development of cataract as well as the cellular changes associated with cataract formation were inhibited by pyruvate. The findings suggest that pyruvate delays the onset of cataract. Such delay appears to be related to its effects against glycation and oxidation. While it prevents sorbitol elevation, the level of this polyol was not osmotically significant.
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