Calcimycin-induced lens epithelial cell apoptosis contributes to cataract formation

Previous studies have shown that calcimycin induces cataract in organ culture. To investigate the mechanism of this induction, the viability of lens epithelial cells in calcimycin (calcium ionophore, A23187)-treated rat lenses were examined. During incubation of lenses with 5 microM calcimycin, apoptotic epithelial cells were found after a 2-hr treatment as determined by terminal deoxynucleotidyl transferase (TdT) labeling. The percentage of apoptotic cells quickly rose as the incubation time increased. After a 12-hr incubation, more than 60% of the lens epithelial cells underwent apoptosis. Prolonged c-fos expression, previously shown to be an indicator of programmed cell death, was also observed during this treatment. DNA fragmentation assays further confirmed that the TdT labeled cells were indeed apoptotic. Under the same incubation conditions, the cultured lenses gradually lost transparency and became completely opaque in about 30 hr. Since the vertebrate lens contains only a single layer of epithelial cells, apoptotic death of these cells activated by calcimycin quickly destroys the lens epithelium, impairs homeostasis of the underlying fiber cells and initiates development of lens opacification.