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Sang-Mok Lee, Eui-Man Jeong, Jinho Jeong, Dong-Myung Shin, Hyun-Ju Lee, Mee-Kum Kim, Won-Ryang Wee, In-Gyu Kim; Cysteamine Decreases Lens Opacity Induced by Selenite in Ex Vivo Rat Lens Culture. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3046.
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The activation of transglutaminase 2 (TG2) by oxidative stress through TGFβ has been reported to play a crucial role in cataract formation. We investigated whether TG2 is involved in selenite-induced cataract formation in ex vivo rat lens culture and whether cysteamine, a chemical inhibitor of TG2, can prevent cataract formation in this model.
Lenses were explanted from 3-week-old male Sprague-Dawley rats and cultured in MEM with sodium selenite (100 μM) and cysteamine (0, 0.125, 0.25, 0.5, 0.75, 1mM). To evaluate the role of TGFβ, pan-specific neutralizing antibody for TGFβ (30μg/mL) instead of cysteamine was added to the MEM in other lenses. Lens images were taken under dark-field microscopy daily until day 8 and lens opacity was quantified using NIH ImageJ software. Intracellular TG2 activity was determined on days 2 and 5. The concentrations of malondialdehyde and glutathione in the lenses were determined.
In cultured rat lenses, selenite induced lens opacity and cysteamine treatment decreased the selenite-induced lens opacity significantly, most effectively at the concentration of 0.5mM (17.62 ± 1.17 in selenite only group vs 13.39 ± 1.42 in cysteamine treatment group at day 8, P=0.029). Selenite caused 4.27 ± 0.74 fold increases in intracellular TG activity on day 5 which was inhibited by cysteamine to 1.11 ± 1.13 fold. The level of total and reduced glutathione was decreased by selenite and partially recovered by the cysteamine treatment. Addition of TGFβ antibody didn’t show significant differences in lens opacity and TG2 activity.
Cysteamine suppresses selenite-induced cataract formation in ex vivo rat lens culture, most effectively at the concentration of 0.5mM and TG2 is involved in the cataractogenesis of this model.
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