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Protective effect of aspirin against dexamethasone-induced cataract in cultured rat lens
Hong Yan1, Jianwei Wang, Bing Liu
1Department of Ophthalmology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Purpose:
To investigate the effect of aspirin on dexamethasone-induced cataract formation in cultured rat lenses.
Methods:
One hundred and forty-eight lenses were divided into 3 groups and cultured in vitro: control (DMEM), cataract (DMEM + 10 microM dexamethasone), aspirin (DMEM + 10 muM dexamethasone + 2 mM aspirin). Following incubation, the transparency of the lenses was evaluated daily using a dissecting microscope. Twelve lenses from each group were homogenized and the activities of enzymes (catalase, superoxide dismutase and lactate dehydrogenase) from supernatants were measured after 1, 3, 5 and 7 days of incubation, respectively. The ultrastructure of lenses from the control and cataract groups was observed on the completion of 7-day incubation.
Results:
Opacity was induced by dexamethasone in the nuclear region of the rat lenses. Lenses in the control group exhibited mist-like opacity and lenses in the cataract group showed dense nuclear opacity, whereas lenses in the aspirin-treated group only had a visible demarcation between nuclear and cortical regions at day 7. The activities of catalase, superoxide dismutase and lactate dehydrogenase in the cataract group decreased in a time-dependent manner. There was no significant loss of enzyme activities in either the control or the aspirin group throughout the incubation period. An orderly arrangement of fiber cells was noted, and the cell membrane, cell junction and organelles were normal in the control group. However, in the cataract group the arrangement of fiber cells was untidy and the lenses contained abnormal-appearing cells. The group exhibited swollen mitochondria, a large number of vacuoles and expanded extracellular lacunae.
Conclusions:
Dexamethasone induces nuclear cataract in the organ-cultured rat lens by chemically modifying proteins, including enzymes. The enzymes, including those that normally eliminate radial oxygen species, could be especially vulnerable. Aspirin significantly inhibits dexamethasone-induced cataract formation by inhibiting inactivation of those enzymes.