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E. Astrom, S.L. Marklund, K. Karlsson, A. Behndig; Involvement of Nitric Oxide in the Formation of In Vitro Diabetic Cataract in Copper-Zinc Superoxide Dismutase Null Mice . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3469.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To elucidate the possible role of nitric oxide (NO) in the formation of In Vitro diabetic cataract in lenses from mice lacking the cytosolic copper-zinc superoxide disnutase (CuZn-SOD). Methods: Lenses from CuZn-SOD null mice (n=41) and wildtype controls (n=54) were dissected and kept in tissue culture medium containing 5.6 or 55.6 mM glucose. For half of the high-glucose lenses, and for a subgroup of the low-glucose lenses, 0.1 mM of the NO synthetase inhibitor L-N(G)-nitroarginine methyl ester (L-NAME) was added to the medium. Cataract formation and lens tissue damage was documented with daily lens photographs and measurements of the leakage of lactate dehydrogenase (LDH) to the medium, and by measuring the lens wet-and dry weight and uptake of [14C]choline at day 6. For a subgroup of the lenses, the superoxide formation was studied by lucigenin-derived chemiluminescence (LDCL) at day 5. Results: When exposed to a high glucose level, lenses from CuZn-SOD null mice show more cataract formation on digital image analysis (P<0.001) and more signs of lens tissue damage in this model, compared to wild type lenses and lenses of either genotype exposed to normal glucose levels. The high-glucose CuZn-SOD lenses with L-NAME added to the medium, however, do not show increased cataractous changes (P>0.12). The other analyses also indicate increased lens tissue damage in the high-glucose CuZn-SOD null lenses without L-NAME. LDCL reveals increased superoxide levels in CuZn-SOD null, compared to wildtype lenses (P=0.002). Conclusions:These findings indicate that the superoxide anion radical participates in the formation of diabetic cataract and that CuZn-SOD may protect against this type of cataract. The protective effect of L-NAME indicates that a combination of superoxide and NO contributes to diabetic cataractogenesis. Peroxynitrite formation is a mechanism by which this hypothetically could be explained.
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